Antibiotics

Spine, 2004 Jul 1, 29(13), 1447 - 51
Spondylocostal dysostosis: thirteen new cases treated by conservative and surgical means; Teli M et al.; STUDY DESIGN: Prospective assessment of a cohort of patients affected by spondylocostal dysostosis . OBJECTIVE: To report on the results of conservative and operative management of spondylocostal dysostosis and, based on this, to propose an assessment and treatment protocol for the condition . SUMMARY OF BACKGROUND DATA: Spondylocostal dysostosis and spondylothoracic dysostosis are subtypes of Jarcho-Levin syndrome, a hereditary condition manifested by vertebral body and related rib malformations . Mortality prevails in spondylothoracic dysostosis because of more severe respiratory compromise . METHODS: Details of prenatal and postnatal diagnosis, history, and management of 13 patients with spondylocostal dysostosis are presented . All patients were treated postnatally with repeated chest physiotherapy . Two patients refractory to conservative treatment underwent surgical intervention: the first had a chest wall reconstruction via a latissimus dorsi flap, the second a posterior spinal instrumented fusion for progressive scoliosis . RESULTS: Prenatal ultrasound in 4 of 13 cases showed full details of vertebral and rib anomalies . Thoracic and lumbar hemivertebrae were most common, leading to congenital scoliosis in 10 of 13 cases . A number of extraskeletal abnormalities were also identified . At an average follow-up of 4.5 years, the survival rate was 100% with a remarkable decrease of the rate of respiratory complications . Surgical treatment in selected cases led to satisfactory results . CONCLUSIONS: Prenatal diagnosis of spondylocostal dysostosis allows exclusion of spondylothoracic dysostosis and aids genetic counseling in quantifying the risk to siblings . Postnatally, prompt management of these patients with physiotherapy leads to prolonged survival . Surgical intervention may then be indicated to stabilize chest wall or spine deformities, with promising results.

Respir Care, 2004 Jul, 49(7), 783 - 92
Evidence-based asthma management; Kallstrom TJ; In 2002 the National Asthma Education and Prevention Program published evidence-based guidelines for the diagnosis and management of asthma, but there are some unresolved asthma-management issues that need further research . For asthmatic children inhaled corticosteroids are more beneficial than as-needed use of beta(2) agonists, long-acting beta(2) agonists, theophylline, cromolyn sodium, nedocromil, or any combination of those . Leukotriene modifiers are an alternative but not a preferred treatment; they should be considered if the medication needs to be administered orally rather than via inhalation . Cromolyn sodium and nedocromil are effective long-term asthma-control medications, but they are not as effective as inhaled corticosteroids . There is insufficient evidence to determine whether cromolyn benefits maintenance of childhood asthma . Cromolyn sodium and nedocromil are alternatives, but not preferred treatments for mild persistent asthma . Cromolyn may be useful as a preventive therapy prior to exertion or unavoidable exposure to allergens . Regular inhalation of corticosteroids controls asthma significantly better than as-needed beta(2) agonists . No studies have examined the long-term impact of regular inhaled corticosteroids on lung function in children <or= 5 years old . As monotherapy, inhaled corticosteroids are more effective than long-acting beta(2) agonists . The asthma-control benefit of inhaled corticosteroids decidedly outweighs the risks from inhaled corticosteroids . There is no high-level evidence that low-to-medium-dose inhaled corticosteroids have ocular toxicity or important effects on hypothalamic-pituitary-adrenal function in children . Antibiotic therapy has no role in asthma management unless there is a bacterial comorbidity, but further research is needed on the relationship between sinusitis and asthma exacerbation . The asthma care plan should include a written asthma action plan for the patient, but there is inadequate evidence as to whether the asthma action plan should be based on symptoms or on peak flow monitoring . There is low-level evidence that helium-oxygen mixture (heliox) may be of benefit in the first hour of an acute asthma attack but less advantageous after that first hour . Metered-dose inhalers are no more or less effective, overall, than other aerosol-delivery devices for the delivery of beta(2) agonists or inhaled corticosteroids, so the least expensive delivery method should be chosen.

Int J Clin Pharmacol Ther, 2004 Jun, 42(6), 307 - 13
Influence of rifampin on serum markers of cholesterol and bile acid synthesis in men; Lutjohann D et al.; OBJECTIVE: It has been demonstrated in preliminary studies that rifampin, a semisynthetic antibiotic and known inducer of hepatic cytochrome P450 3A4, reduces serum concentrations of total bile acids only in individuals with liver disease and elevated serum bile acid levels . METHODS: We studied the effect of rifampin on concentrations of surrogate serum markers of cholesterol and bile acid synthesis as well as of cholesterol absorption in 10 male subjects before and after administration of rifampin (600 mg/day) for 6 days . Cholesterol and its precursors were analyzed by gas-liquid chromatography (GLC), bile acid intermediates and individual bile acids by isotope-dilution methods using GLC-mass spectrometry (MS) or by high-performance liquid chromatography (HPLC) . RESULTS: Treatment with rifampin resulted in a 70% increase (p = 0.008) of the serum concentration of the bile acid precursor 7alpha-hydroxy-4-cholesten-3-one, which is a marker for bile acid production . Serum total cholesterol was not altered, however, treatment with rifampin elevated the ratio of lathosterol to cholesterol, an indicator of cholesterol synthesis, by 23% (p = 0.037) . Interestingly, serum concentration of total bile acids decreased slightly by 29% (p = 0.022), mainly due to a lowering of the secondary bile acid, deoxycholic acid (-60%; p = 0.005) . CONCLUSION: A 6-day treatment with rifampin induces a reduction of deoxycholic serum concentrations in healthy men associated with a moderate increase of serum markers of bile acid and endogenous cholesterol synthesis.

J Heart Valve Dis, 2004 May, 13(3), 494 - 9; discussion 499-500
Could 37 degrees C storage temperature extend homovital valve allograft viability?
Baric D, Cebotari S, Mertsching H, Leyh R, Haverich A.
BACKGROUND AND AIM OF THE STUDY: Preservation of allograft valves is the most important determinant of their durability . Unprocessed, homovital valve allografts stored at 4 degrees C in nutrient medium have provided superior mid-term results over routinely used cryopreserved or antibiotic-sterilized allografts . As storage temperature may alter viability, it was hypothesized that allograft storage at 37 degrees C may maintain greater viability over time . METHODS: Porcine aortic (n = 10) and pulmonary valve conduits (n = 10) were harvested under sterile conditions . Valve leaflets and sinus walls were separated, and each was divided into two specimens, which were stored in modified culture medium at 4 degrees C and 37 degrees C, respectively . Cell viability was tested by monitoring metabolic activity at 37 degrees C at days 1, 3, 7, 10, and 14 . The proliferative ability of cells isolated from valve leaflets was assessed after 14 days by cell culture . Sterility testing of the storage medium was also carried out . RESULTS: Valve leaflet cells and sinus wall cells had significantly higher metabolic activity when stored at 37 degrees C . The median number of isolated cells at 4 degrees C was 3,231.5 (range: 422-3,844), and at 37 degrees C was 8,317.50 (range: 4,329-8,650) . The storage medium was sterile in all cases . CONCLUSION: Storage at 37 degrees C significantly improved valve allograft cell metabolic activity and viability compared with storage at 4 degrees C for up to 14 days . The lower concentration of antibiotics did not affect the sterility of tissues stored at 37 degrees C.

Amino Acids, 2004 Jun, 26(3), 283 - 9 Epub 2003 Oct 17.
Synthesis and investigation of a new cyclo (Nalpha-dipicolinoyl) pentapeptide of a breast and CNS cytotoxic activity and an ionophoric specificity; Abo-Ghalia M et al.; A new acylated cyclopentapeptide namely, Cyclo-( N(alpha)-dipicolinoyl)- bis-{ L-Leu-DL-Nval}- L-Lys OMe (5) was suggested and synthesized . The structural conception of 5 was rationalized by analogy to the structural features of some known cyclodepsipeptides exemplified by the antibiotic and DNA intercalator actinomycin D (NSC: 3053), the ionophore and anti-HIV enniatin B (NSC: 692895) and the ionophore and antibiotic valinomycin (NSC: 630175) . The cyclopeptide 5 was chemically synthesized, starting from its linear tetrapeptide ester precursor 2 by coupling L-lysine methyl ester to the prepared tetrapeptide acid 3 or hydrazide 4 via the mixed anhydride or azide method, respectively . A cytotoxic activity (cell killing) in both breast (NCF7) and CNS (SF-268) cell lines NCI, USA) was realized for 5, while less active cytotoxic profile was determined for 2 . Moreover, we have recently reported general ionophoric and sensor characteristics particularly, for Pb (II) ions for both 5 and 2 . Correlation between the cytotoxic activity and the ionophoric potency is a matter of future investigations.

Ann Hematol, 2004 Sep, 83(9), 573 - 7 Epub 2004 Jun 19.
Ganciclovir-related neutropenia after preemptive therapy for cytomegalovirus infection: comparison between cord blood and bone marrow transplantation; Tomonari A et al.; We studied ganciclovir (GCV)-related neutropenia after preemptive therapy for cytomegalovirus infection: 9 of 17 (53%) cord blood transplantation (CBT) patients and 18 of 20 (90%) bone marrow transplantation (BMT) patients developed GCV-related neutropenia with an absolute neutrophil count (ANC) of less than 1,000/microl . Among the patients who did not receive granulocyte colony-stimulating factor, 2 (13%) and 1 (7%) CBT patients, and 10 (56%) and 8 (44%) BMT patients, developed neutropenia with an ANC of less than 500 and 250/microl, respectively . The incidences of neutropenia in patients with an ANC of less than 1,000, 500, and 250/microl were significantly lower after CBT in comparison with BMT . Two BMT patients, but no CBT patients, developed neutropenic fever, and both patients recovered after antibiotic therapy . In CBT patients, a creatinine clearance rate of less than 50 ml/min and an absence of steroid therapy were associated with a greater incidence of GCV-related neutropenia . No risk factors for GCV-related neutropenia were found in BMT patients . These results suggest that GCV may be less toxic to myeloid progenitor cells from cord blood than those from bone marrow.

J Endod, 2004 Jul, 30(7), 541 - 7
Management of extra oral sinus cases: a clinical dilemma; Mittal N et al.; The cutaneous sinus tract of dental origin is an uncommon but well documented condition . Its diagnosis is not always easy unless the treating clinician considers the possibility of its dental origin . Such patients may undergo multiple surgical excisions, biopsies, and antibiotic regimens, but all of them fail with the recurrence of the sinus tract . This is because the primary etiology is incorrectly diagnosed . This case report describes the treatment of four patients presenting with variable complaints of pain and purulent or hemorrhagic discharge from lesions of the face . Clinical and radiographic examination revealed carious teeth with radiolucent areas indicating chronic periradicular abscess . The teeth were restorable, so nonsurgical endodontic therapy was performed in all of them . No systemic antibiotic therapy was provided . The patients responded well, and the cutaneous lesions healed uneventfully . Improper diagnosis can lead to needless loss of teeth that can be otherwise maintained through timely and proper management.

Prev Vet Med, 2004 Jun 10, 64(1), 27 - 40
Within-herd spread of contagious bovine pleuropneumonia in Ethiopian highlands; Lesnoff M et al.; Contagious bovine pleuropneumonia (CBPP) is a major threat for cattle health and production in Africa . This disease is caused by the small-colony type of Mycoplasma mycoides subspecies mycoides (MmmSC) . Transmission occurs from direct and repeated contacts between sick and healthy animals . Veterinary services recently reported a resurgence of CBPP in the province of West Wellega, in the Ethiopian highlands . A research program was set up to estimate the epidemiological parameters of the within-herd infection spread . A follow-up survey was implemented in 71 sampled herds of the Boji district (West Wellega province) . Fifteen herds were classified as newly infected and used in a serological- and clinical-incidence study . The overall 16-month cumulative sero-incidence risk was 34% . Clinical cases were recorded for 39% of the seropositive cattle; case-fatality risk was 13% . There was no evidence of benefit on infection spread of CBPP-control measures used locally by farmers (isolation or antibiotic treatments of sick animals) . This might be related to a lack of power in the statistical analyses or to a quality problem for the medications used (and more generally, for health-care delivery in the Boji district).

Nefrologia, 2004, 24 Suppl 3, 16 - 20
{Fever and cavitary infiltrate in a renal transplant recipient}; Rocamora N et al.; Aspergillus infection is a rare but devastating complication following organ transplantation with high mortality rate . Aspergillus fumigatus is the most common cause of invasive aspergillosis . This fungus is present in the environment worldwide . Aspergillus infection is mainly acquired by inhalation of spores and several nosocomial infections in transplant recipient have been associated with construction work at hospitals . Risk factors for invasive aspergillosis include administration of steroid boluses, history of cytomegalovirus infection, neutropenia and prolonged antibiotic use after transplantation . Successful treatment depends on three factors: early diagnosis, aggressive antifungal therapy and decrease or removal of immunosuppression . Amphotericin deoxycholate has been the standard treatment for many years but lipid preparations for amphotericin are now used due to their significantly fewer adverse effects . A number of new antifungal drugs are now being developed including new azoles such as voriconazol and echinocandin . Invasive aspergillosis has a high mortality rate more than 95% when cerebral dissemination is demonstrated . We report the case of a 47 years old woman who received a cadaveric renal graft and developed pulmonary aspergillosis with fulminant cerebral dissemination two months later . The diagnosis of pulmonary aspergillosis was by culture isolation obtained from bronchioalveolar lavage . Removal of immunosuppresive agents and liposomal amphotericin B therapy were started shortly after admission . Brain CT scan performed on the 12th day showed cerebral dissemination . The recipient died two days later . Our patient had several risk factors such as the administration of steroid boluses and cytomegalovirus infection . Invasive aspergillosis must be always included in the differential diagnosis of fever and pulmonary disease in the renal transplant recipient.

Proc Natl Acad Sci U S A, 2004 Jul 6, 101(27), 10036 - 41 Epub 2004 Jun 24.
Mass spectrometric characterization of a three-enzyme tandem reaction for assembly and modification of the novobiocin skeleton; Pi N et al.; The tripartite scaffold of the natural product antibiotic novobiocin is assembled by the tandem action of novobiocin ligase (NovL) and novobiocic acid noviosyl transferase (NovM) . The noviosyl ring of the tripartite scaffold is further decorated by a methyltransferase (NovP) and a carbamoyltransferase (NovN), resulting in the formation of novobiocin . To facilitate kinetic evaluation of alternate substrate usage by NovL and NovM toward the creation of variant antibiotic scaffolds, an electrospray ionization/MS assay for obtaining kinetic measurements is presented for NovL and NovM separately, in each case with natural substrate and the 3-methyl-4-hydroxybenzoic acid analog . Additionally, assays of tandem two-enzyme (NovL/NovM) and three-enzyme (NovL/NovM/NovP) incubations were developed . The development of these assays allows for the direct detection of each intermediate followed by its utilization as substrate for the next enzyme, as well as the subsequent formation of final product as a function of time . This MS tandem assay is useful for optimization of conditions for chemoenzymatic generation of novobiocin and is also suitable for evaluation of competitive usage of variant substrate analogs by multiple enzymes . The studies presented here serve as a platform for the subsequent expansion of the repertoire of coumarin-based antibiotics.

J Anim Sci, 2004 Jun, 82(6), 1764 - 72
Spray-dried plasma improves growth performance and reduces inflammatory status of weaned pigs challenged with enterotoxigenic Escherichia coli K88; Bosi P et al.; We investigated whether spray-dried plasma (SDP) improved growth and health of piglets challenged with enterotoxigenic Escherichia coli K88 (ETEC) . Forty-eight pigs weaned at 21 d (BW = 4.88 +/- 0.43 kg) received one of four diets containing 6% SDP or fish proteins (as-fed basis) either nonmedicated (SDP-NM and FP-NM diets) or medicated with 0 or 250 mg/kg of colistine + 500 mg/kg of amoxycycline (SDP-M and FP-M diets), for 15 d . On d 4, pigs were orally challenged with ETEC . On d 15, eight pigs per dietary group were killed, blood and saliva were collected for analysis of K88 fimbriae-specific immunoglobulin (Ig)-A, and jejunum was removed for villi preparation, histological analysis, and cytokine expression . The presence or absence of K88 receptors (K88+ and K88- pigs respectively) was determined by villous adhesion assay . Effects of protein source on ADG (P = 0.04) and ADFI (P < 0.01), as well of medication on ADFI (P < 0.02), of all pigs were observed . In sacrified pigs, there was an effect of protein source on ADG (P = 0.03) and ADFI (P < 0.001), as well an interaction between medication and presence of K88 receptor (P = 0.02) for feed:gain ratio . Plasma K88 specific IgA were low in all K88 pigs and higher in K88+ pigs fed FP-NM compared with all the other groups (P < 0.05), except SDP-M . An interaction was found among protein source, medication, and presence of K88 receptors (P = 0.04) . Saliva IgA concentrations were high in all pigs fed FP-NM and low in all other pigs . Jejunum of pigs fed FP-NM showed some ulcerations, edema, and mild inflammatory cell infiltration (ICI) . In pigs fed FP-M, edema was reduced . Conversely, only a mild ICI was observed in pigs fed SDP-NM and SDP-M . Crypt depth was increased in K88+ pigs fed SDP-NM and an interaction between protein source and presence of K88 receptors was observed (P < 0.05) . Expressions of tumor necrosis factor-alpha and interleukin (IL)-8 were lower in pigs fed SDP-NM and SDP-M than in those fed FP-NM and FP-M, either K88- or K88+ (P < 0.01) . In pigs fed FP diets, expression of IL-8 tended to increase (P = 0.08) in K88+ compared with K88- subjects . Expression of interferon-gamma increased in K88 and K88+ pigs fed FP-M as compared with other pigs (P < 0.01) . These results indicate that feeding with SDP improved growth performance and protected against E . coli-induced inflammatory status, and suggest that use of SDP-NM can be considered a valid antibiotic alternative.

Tsitologiia, 2003, 45(8), 804 - 11
{Amphotericin B channel conductance inactivation}; Ibragimova VKh et al.; Effects induced in bilayer lipid membranes by amphotericin B and its alkyl derivatives was analysed . Inactivation of the antibiotic-dependent multichannel membrane conductance was discovered . Kinetics of membrane conductivity was shown to depend on the antibiotic concentration in the membrane . At concentrations between 10(-8) and 10(-7) M, the resulting conductance appeared to the transient . We suggest that the phenomenon of biphasic kinetics of membrane conductance is the result of a consecutive transformation of polyene channels in the membrane: half-pores are assembled on either side of membrane-nonconducting 1; two half-pores combine to build up a conducting channels-conducting 2, and the conducting channels are disassemled to monomers and nonconducting self-associated forms inside the membrane-disassembled state (nonconducting 3) . To explain the transient characteristics of the induced conductance, it is proposed that the antibiotic, present in the solution under self-associated form, binds the membrane and forms pores, then dissociates in the bilayer in a non-active monomeric form . The existence of definite monomers and nonconducting self-associated forms of amphotericin B molecules inside the membrane was estimated from the dependence of kinetic conductance of lipid membranes of amphotericin B and its alkyl derivatives, when the antibiotics are washed out from aqueous medium . Equilibrium between different antibiotic assemblies inside the membrane was demonstrated by the kinetics of conductance decrease following washing the antibiotic . Using circular dichroism measurements, we observed that amphotericin B alkyl derivatives were in self-associated form being susceptible to form pores across cholesterol-containing membranes . The phenomenon of biophasic kinetics was observed only in the cholesterol-containing membrane . The substitution of membrane cholesterol for ergosterol provides monotonic kinetics of membrane conductance at any antibiotic concentration.

Biosci Biotechnol Biochem, 2004 Jun, 68(6), 1345 - 52
Identification and cloning of the gene involved in the final step of chlortetracycline biosynthesis in Streptomyces aureofaciens; Nakano T et al.; For chlortetracycline biosynthesis in Streptomyces aureofaciens, the final reduction step is essential to give an antibiotic activity to its intermediate, which is catalyzed by tetracycline dehydrogenase with 7,8-dedimethyl-8-hydroxy-5-deazariboflavin (FO) as a cofactor . We identified and cloned the gene, which is essential for the biosynthesis of 6-demethyltetracycline and participates in the final step of its biosynthesis, from the genomic DNA of the 6-demethyltetracycline producer S . aureofaciens HP77 . DNA sequence analysis revealed that the gene (tchA) had an open reading frame of 455 amino acids with an estimated molecular mass of 48.1 kDa . Southern hybridization analysis revealed that the tchA gene was located external to the chlortetracycline biosynthetic gene cluster in the genome . A conserved domain search of protein sequence databases indicated that TchA showed a similarity to FbiB, which is involved in the modification of FO in Mycobacterium bovis.

Antimicrob Agents Chemother, 2004 Jul, 48(7), 2538 - 43
Effects of fluoroquinolones on the migration of human phagocytes through Chlamydia pneumoniae-infected and tumor necrosis factor alpha-stimulated endothelial cells; Uriarte SM et al.; The anti-inflammatory activities of three quinolones, levofloxacin, moxifloxacin, and gatifloxacin, were investigated with an in vitro model of transendothelial migration (TEM) . Human umbilical vein endothelial cells (HUVEC) were seeded in Transwell inserts, treated with serial dilutions of antibiotics, infected with Chlamydia pneumoniae, or stimulated with tumor necrosis factor alpha (TNF-alpha) . Neutrophils or monocytes were also preincubated with serial dilutions of each antibiotic . TEM was assessed by light microscopic examination of the underside of the polycarbonate membrane, and levels of interleukin-8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) were measured by enzyme-linked immunosorbent assay . In HUVEC infected with C . pneumoniae or stimulated with TNF-alpha, all fluoroquinolones significantly decreased neutrophil and monocyte TEM, compared to antibiotic-free controls . Moxifloxacin and gatifloxacin produced a significant decrease in IL-8 in C . pneumoniae-infected and TNF-alpha-stimulated HUVEC; however, moxifloxacin was the only fluoroquinolone that produced a significant decrease in MCP-1 levels under both conditions . Results from this study indicate similarities in the anti-inflammatory activities of these fluoroquinolones, although no statistically significant decrease in chemokine secretion was observed when levofloxacin was used . Mechanisms of neutrophil and monocyte TEM inhibition by fluoroquinolone antibiotics are unknown but may be partially due to inhibition of IL-8 and MCP-1 production, respectively.

Antimicrob Agents Chemother, 2004 Jul, 48(7), 2471 - 6
Impact of fluconazole prophylaxis on cortisol levels in critically ill surgical patients; Magill SS et al.; Fluconazole is widely used in the intensive care unit for prevention and treatment of fungal infections . Case reports have described an association between fluconazole and adrenal dysfunction, an important cause of morbidity and mortality in critically ill patients . We sought to determine whether 400 mg of fluconazole per day administered to critically ill surgical patients was associated with a reduction in cortisol levels . Cortisol levels were measured in stored plasma specimens drawn from 154 critically ill surgical patients randomized in 1998-1999 to receive fluconazole or placebo for the prevention of candidiasis . The primary outcome measure was the median plasma cortisol level > or =1 day after study drug initiation (MPCL) . Secondary outcomes were adrenal dysfunction, defined as an MPCL of <15 microg/dl, changes in cortisol levels over time, and mortality . The median MPCL was 15.75 microg/dl (interquartile range {IQR}, 11.65 to 21.33 microg/dl) in 79 patients randomized to fluconazole and 16.71 microg/dl (IQR, 11.67 to 23.00 microg/dl) in 75 patients randomized to placebo (P = 0.52) . Patients randomized to fluconazole did not have significantly increased odds of adrenal dysfunction compared to patients randomized to placebo (odds ratio, 0.98; 95% confidence interval, 0.48 to 2.01) . Randomization to fluconazole was not associated with a significant difference in cortisol level changes over time . Mortality was not different between patients with and without adrenal dysfunction, nor was it different between patients with adrenal dysfunction who were randomized to fluconazole and those randomized to placebo . Fluconazole prophylaxis in this population of critically ill surgical patients did not result in significant adrenal dysfunction.

Eur Rev Med Pharmacol Sci, 2003 Sep-Oct, 7(5), 127 - 30
A new approach for the treatment of bacterial vaginosis: use of polyhexamethylene biguanide . A prospective, randomized study; Gerli S et al.; BACKGROUND: Bacterial vaginosis (BV) is the most common vulvovaginal infection and represents the 35% of all the infections occurring in women in the reproductive age . It is well recognised that serious forms of BV can induce several complications among women undergoing gynaecologic or obstetric surgery, having pelvic inflammatory diseases, temporary or absolute infertility, miscarriage and abortion . At present, the clinical treatment of choice of BV is the use of systemic or local (gel or cream) metronidazole and clindamycin, though systemic use has some limitations due to side-effects and contraindications . Polyhexamethylene biguanide (PHMB) is a new bi-biguanide compound having a broad spectrum activity and low toxicity, that have been successfully utilized in ophthalmology and dentistry . Aim of this study was to evaluate the efficacy and tolerability of a single-dose vaginal administration of a PHMB vaginal gel in the treatment of BV in comparison to clindamycin vaginal cream . METHODS: One-hundred and ten patients affected by BV were treated with PHMB vaginal gel in single administration or clindamycin vaginal cream 1 daily administration for 7 days . RESULTS: We demonstrated the therapeutic efficacy of mono-dose administration of a vaginal solution containing PHMB in BV treatment; this efficacy is similar to the one shown in antibiotic therapy . Furthermore, this product was well tolerated by all treated patients . CONCLUSIONS: Mono-dose PHMB treatment should be regarded as the therapy of choice for BV, using clindamycin and metronidazole only for relapses treatment.

Ann Surg, 2004 Jul, 240(1), 28 - 37
The diminishing role of surgery in the treatment of gastric lymphoma; Yoon SS et al.; OBJECTIVE: This article reviews the pathogenesis, diagnosis, and treatment of patients with primary gastric lymphoma, with special attention to the changing role of surgery . SUMMARY BACKGROUND DATA: Primary gastric lymphomas are non-Hodgkin lymphomas that originate in the stomach and are divided into low-grade (or indolent) and high-grade (or aggressive) types . Low-grade lesions nearly always arise from mucosa-associated lymphoid tissue (MALT) secondary to chronic Helicobacter pylori (H . pylori) infection and disseminate slowly . High-grade lesions may arise from a low grade-MALT component or arise de novo and can spread to lymph nodes, adjacent organs and tissues, or distant sites . METHODS: A review of the relevant English-language articles was performed on the basis of a MEDLINE search from January 1984 to August 2003 . RESULTS: About 40% of gastric lymphomas are low-grade, and nearly all these low-grade lesions are classified as MALT lymphomas . For low-grade MALT lymphomas confined to the gastric wall and without certain negative prognostic factors, H . pylori eradication is highly successful in causing lymphoma regression . More advanced low-grade lymphomas or those that do not regress with antibiotic therapy can be treated with combinations of H . pylori eradication, radiation therapy, and chemotherapy . Nearly 60% of gastric lymphomas are high-grade lesions with or without a low-grade MALT component . These lymphomas can be treated with chemotherapy and radiation therapy according to the extent of disease . Surgery for gastric lymphoma is now often reserved for patients with localized, residual disease after nonsurgical therapy or for rare patients with complications . CONCLUSION: The treatment of gastric lymphoma continues to evolve, and surgical resection is now uncommonly a part of the initial management strategy.

Med Wieku Rozwoj, 2003 Oct-Dec, 7(4 Pt 2), 547 - 55
{Pharmacokinetics of netilmicin in neonates}; Piekarczyk A et al.; Our goal was to perform a pharmacokinetic analysis of netilmicin to develop the optimum dosage regimen of this antibiotic in premature neonates hospitalized in Neonate Intensive Care Unit of the Institute of Mother and Child in Warsaw . MATERIALS AND METHODS: The pharmacokinetics of netilmicin was studied in 80 neonates, divided for analysis into three groups according to gestational age: group I - 10 full-term neonates (b.w . 3225 +/-502 g); group II - 35 premature neonates between 29-32 weeks (b.w . 1134+/-311 g); and group III - 35 premature neonates between 23-28 weeks (b.w . 910 +/-243 g) . The whole studied group of neonates was initially given i.v . netilmicin every 24 h, then the dosing interval for the safety reasons was prolonged to 48 h in the premature group . The neonates received netilmicin in the following doses: group I - mean dose 6.2 +/-0.42 mg/kg; group II - 5.911+/-0.529 mg/kg and group III - 6.014+/-0.313 mg/kg . Serum netilmicin concentrations were determined by fluorescence polarization immunoassay (FPIA) - TD(x)FL(x) (Abbott) . RESULTS: The mean of pharmacokinetic parameters for groups I, II, and III were defined respectively: t(0.5) (h): 7.14+/-1.88, 12.68+/-4.26, 15.98+/-5.9; AUC0-( (microg x h/ml): 149+/-41, 303+/-100, 401+/-172; Cl/kg (l/h/kg): 0.748+/-0.24, 0.371+/-0.13, 0.289+/-0.1; MRT0-( (h): 6.3+/-2.8, 10.8+/-6.3, 15.5+/-9.3; V(dss) (l/kg): 0.75+/-0.24, 0.59+/-0.52, 0.44+/-0.19 . The obtained mean netilmicin serum concentrations (microg/ml) were: once-a-day dosage: C(max) - 10.25+/-2.616 (group I), 12.2+/-2.65 (group II), 12.9+/-2.77 (group III); C(min) - 1.158+/-0.657 (group I), - 2.65+/-1.02 (group II), 3.23+/-1.42 (group III); once-a-48 h dosage: C(max) - 11.7+/-1.09 (group II), 13.9+/-6.53 (group III); C(min) - 1.09+/-0.64 (group II), 1.74+/-0.98 (group III) . CONCLUSIONS: 1 . All the calculated pharmacokinetic parameters in the premature neonate groups (group II and III) significantly differs from the parameters calculated for full-term neonates . 2 . Significant correlations were obtained between birth weight, gestational age and all the calculated pharmacokinetic parameters in all the groups of neonates . 3 . The obtained results indicated that the use of the dosing schedule of netilmicin with the dose intervals of 48 h in premature neonates should guarantee adequate peak and trough levels without the need of routine monitoring of each patient in the premature neonate group except the very low weight neonates . Detection of the specific sensitivity of lymphocytes T during the diagnosis of food allergy.

Dis Aquat Organ, 2004 Apr 21, 59(1), 75 - 8
Appendage deformity syndrome--a nutritional disease of Macrobrachium rosenbergii; Kumar AR et al.; Culture of the freshwater prawn Macrobrachium rosenbergii as an alternative to penaeid shrimp has recently increased in coastal areas of southern India in order to avoid numerous problems, particularly with white spot syndrome virus (WSSV) . However, M . rosenbergii culture is now threatened by a new disease, appendage deformity syndrome (ADS), that also results in high mortality . Analysis of ADS prawns for viruses such as WSSV, monodon baculovirus (MBV) and infectious hypodermal and hematopoeitic necrosis virus (IHHNV) gave negative results . ADS prawns were also negative for bacterial pathogens and affected animals did not respond to antibiotic therapy . A study of potential nutritional deficiency revealed that carotenoid supplementation in the diet led to a significant decrease in ADS prawns.

Pediatr Pulmonol, 2004 Aug, 38(2), 129 - 34
Cyproheptadine is an effective appetite stimulant in cystic fibrosis; Homnick DN et al.; Chronic pulmonary infection and intestinal malabsorption often lead to malnutrition in children and adults with cystic fibrosis (CF) . Appetite stimulants, along with provision of adequate calories, may aid in overcoming nutritional deficits, allowing a better prognosis . We undertook a trial of cyproheptadine hydrochloride (CH) to determine its effectiveness as an appetite stimulant in 18 adults and children with CF . This was a 12-week, randomized, double-blind, controlled trial of CH vs . placebo . Eighteen subjects with documented CF (sweat or genetics positive), minimum age of 5 years, and ideal body weight for height <100% were entered, and 16 completed the study . Subjects were seen at baseline and every 4 weeks . Measures included baseline demographics, Shwachman score, anthropometrics (weight, height, body mass index, skin folds, and body composition by bioelectric impedance analysis), spirometry, caloric intake, days of oral (PO) and intravenous (IV) antibiotics, and a symptom and satisfaction survey . Subjects in the CH group showed significant increases in weight (mean 3.45 kg vs . 1.1 kg in the placebo group), height, BMI percentiles, ideal body weight/height, weight for age z-scores, and fat and fat-free mass . There were no changes or differences in PO or IV antibiotic use or spirometric changes . No significant side effects except transient mild sedation occurred in the CH group . Patient acceptance was good . In conclusion, CH appears to be an effective appetite stimulant with minimal side effects in children and adults with CF .

Patient Educ Couns, 2004 Jul, 54(1), 21 - 5
Acne vulgaris: myths and misconceptions among patients and family physicians; Brajac I et al.; The objective of the study was to evaluate the health beliefs and knowledge about acne among acne patients and family physicians . A total of 100 patients referred to a dermatologist for management of acne vulgaris and 120 family physicians completed questionnaires . The questionnaires consisted of questions about health beliefs, the natural course of the disease, the causes of acne, and a set of questions about the knowledge of acne therapy . Acne was considered as a trivial and transitory condition by 52% of the acne patients and 44% of the family physicians . The overall score of correct answers pertaining to the causes of acne among the acne patients and family physicians was 11 and 15%, respectively . The percentage of correct answers regarding the natural course of the disease was 6% for both subsets of subjects . Acne was believed to be curable by 96% of acne patients . Most patients (66%) believed that acne would improve immediately after the first treatment . The knowledge of isotretinoin teratogenecity was reasonable among family physicians (55% correct answers), but it was much lower for other side effects (9%) . The overall score of correct answers regarding antibiotic therapy among family physicians was only 21% . Impact of the disease was underestimated by family physicians and also by acne patients . Overall knowledge pertaining to the causes, natural course and therapy was very low . Myths and misconceptions still exist among patients but also among family physicians.

Diabet Med, 2004 Jul, 21(7), 705 - 9
Swab cultures accurately identify bacterial pathogens in diabetic foot wounds not involving bone; Slater RA et al.; AIMS: Current clinical practice assumes swab cultures from wounds are unreliable . However, this assumption is based upon data culled only from wounds in which osteomyelitis and/or gangrene were present . This study aimed to re-evaluate the accuracy of swab cultures vs . deep tissue cultures in diabetic wounds of varying depth and severity . METHODS: A total of 60 infected diabetic foot wounds were cultured . Two specimens were taken from each wound: superficial swab before debridement and deep tissue specimen towards the end of surgical debridement . RESULTS: In 37 wounds (62%), the micro-organisms isolated from the swab specimen and those isolated from the deep tissue specimen were identical . In another 12 wounds (20%), the swab culture contained all micro-organisms isolated from the deep tissue culture, but also contained additional micro-organisms . Analysis according to the depth of the wound, demonstrated that swabs identified all micro-organisms isolated from the deep tissue specimens in 36/40 wounds (90%) that did not extend to bone as opposed to 13/20 wounds (65%) that extended to bone . CONCLUSIONS: Swab cultures are valuable in identifying pathogens in diabetic foot wounds when bone is not involved . When surgical debridement is contraindicated or delayed, swab cultures can be used to select appropriate antibiotic therapy.

Bone Marrow Transplant, 2004 Jul, 34(1), 51 - 6
A randomized trial of amifostine as a cytoprotectant for patients receiving myeloablative therapy for allogeneic hematopoietic stem cell transplantation; Hwang WY et al.; We initiated a randomized study of amifostine (the organic thiophosphate formerly known as WR-2721) given to patients during myeloablative conditioning therapy for allogeneic bone marrow transplantation . Amifostine was given at a dose of 1000 mg/day of conditioning and was well tolerated if attention was given to serum calcium levels, blood pressure and antiemetics . Since August 1998, 60 patients (30 on each arm) have completed the study . There was no significant difference in the days to neutrophil or platelet engraftment in either arm of the study . Significantly, the duration of grade I-IV mucositis was decreased in the group that received amifostine (P=0.02) . Also grade III or IV infections (P=0.008), duration of antibiotic therapy (P=0.03) and duration of fever (P=0.04) were significantly reduced with amifostine . However, there were no differences in the incidence of grade III or IV mucositis, liver toxicity or renal toxicity . There were also no differences in early mortality, relapse and long-term survival . We conclude that amifostine, while reducing the duration of mucositis and infections (possibly through some preservation of gut mucosal integrity), has a modest effect in allogeneic bone marrow transplants given the multiplicity of factors influencing organ toxicity and survival in this setting.

Plant Physiol, 2004 Jun, 135(2), 709 - 14
Fluorescent screening of transgenic Arabidopsis seeds without germination; Wei S et al.; In this paper, we describe a reliable method for the screening and selection of Arabidopsis transgenic seeds within minutes without germination . Expression of the Aspergillus niger beta-glucosidase gene BGL1 in the plant's endoplasmic reticulum was used as a visual marker, together with 4-methylumbelliferyl-beta-D-glucopyranoside (MUGluc) as a substrate . Subsequent to incubation in a solution of MUGluc at room temperature for 2 to 15 min, transgenic seeds expressing BGL1 demonstrated a distinct fluorescent signal under UV light . Optimal screening conditions at room temperature were achieved between 75 and 450 microm MUGluc, at a pH of 2.5 to 5.0 and 2 to 5 min of incubation . No significant loss of viability was detected in transgenic seeds that were redried and stored for 45 d after incubation in MUGluc solution for 2 to 150 min . Transgenic plants expressing BGL1 displayed normal phenotypes relative to the wild type . Selection frequency was 3.1% +/- 0.34% for the fluorescence selection method, while kanamycin resistant selection resulted in only 0.56% +/- 0.13% using the same seed batch . This novel selection method is nondestructive, practical, and efficient, and eliminates the use of antibiotic genes . In addition, the procedure shortens the selection time from weeks to minutes.

Emerg Med J, 2004 Jul, 21(4), 446 - 8
Limited usefulness of initial blood cultures in community acquired pneumonia; Corbo J et al.; OBJECTIVE: The incidence of community acquired pneumonia (CAP) is about 4 million cases per year, with a hospitalisation rate of 20% . In non-immunocompromised patients hospitalised for CAP the rate of bacteraemia is less than 7% with predictable pathogens . Despite this, guidelines still recommend use of blood cultures (BCs) to direct treatment . This study tested the primary hypothesis that the proportion of false positive BCs would exceed the proportion of true positives . A secondary aim was to quantify the frequency with which antibiotic therapy was changed based on BC results . METHOD: Consecutive adults hospitalised from an urban emergency department (ED) with CAP between January 1999 and March 2001 were assessed retrospectively for study eligibility . Those with an infiltrate consistent with pneumonia on the admission chest radiograph and at least one set of BCs taken in the ED before antibiotics were given were entered into the study . Patients hospitalised within the previous two weeks, nursing home residents, and immunosuppressed patients were excluded . RESULTS: 821 patients were admitted for CAP and 355 met inclusion criteria . The proportion of false positive BCs (10%) exceeded the proportion of true positives (9%), by 1% (95%CI -3.3% to 5.5%) . Antibiotic therapy was changed on the basis of BC results in 5% of patients (95%CI 3% to 8%) . CONCLUSION: The rate of false positive BCs in patients hospitalised with CAP is similar to the rate of true positives . BCs only infrequently lead to changes in antibiotic therapy, and in no instance were therapeutic changes driven by detection of resistant organisms . The results question the utility of routine BCs in immunocompetent patients with CAP.

Enferm Infecc Microbiol Clin, 2004 May, 22(5), 279 - 85
{Indications for antifungal treatment in intensive care unit patients}; Alvarez-Lerma F et al.; INTRODUCTION: This study investigates the indications for antifungal treatment in patients admitted to intensive care units (ICUs) in Spain and determines the frequency at which each individual drug is prescribed . METHODS: Observational, multicenter study including all patients admitted to 64 ICUs on 23 March, 22 June, and 16 November, 1999 . The use of antifungal agents and the criteria for indicating antifungal therapy were assessed . Patients were classified as colonized or infected by fungi . RESULTS: In 180 (11.5%) of the 1562 patients included in the study, 219 courses of treatment with antifungal agents were prescribed (antifungal therapy rate of 14 per 100 patients) . Fluconazole was the antifungal agent most frequently used, both in infected and colonized patients . The most common reasons for prescribing antifungal therapy were as follows: candiduria (21.9%), severe sepsis with no response to antibiotic therapy (19.6%), and evidence of fungi in two or more non-invasive sites (16.9%) . Candidemia was the reason for antifungal treatment in 17 (7.9%) cases . Proven fungal infections accounted for 21.1% of indications . Variables significantly associated with the use of antifungal agents included underlying disease, severity of illness according to the APACHE II score, chronic liver disease, solid tumor, immunosuppression, and organ transplantation . Significant extrinsic risk factors for antifungal therapy included treatment with corticoids, chemotherapy, mechanical ventilation, urgent and/or elective surgery, and previous use of antibiotics . CONCLUSIONS: A total of 11.5% of patients included in the study were given one or more treatment courses with antifungal agents . Antifungal treatment was prescribed in proved fungal infections in only 21.1% of cases . Fluconazole was the antifungal agent most frequently used.

Eur J Ophthalmol, 2004 May-Jun, 14(3), 185 - 92
Repeated probing results in the treatment of congenital nasolacrimal duct obstruction; Singh Bhinder G et al.; PURPOSE: To assess the results of our protocol of repeated probing for the treatment of congenital nasolacrimal duct obstruction in various presentations . METHODS: A total of 1600 patients (1748 eyes) with congenital dacryocystitis (850 boys, 750 girls; age range, 1 month to 48 months {mean 16.54 +/- 12.21 months}) were included . Diagnosis was confirmed by history of tearing, crusting of lids, and a boggy swelling over inner canthal region, which on pressure ejected mucopurulent discharge through punctum . Antibiotic eye drops were instilled five times a day for a week in affected eyes after the mother pressed the sac area and cleaned the discharge . The cases that were not relieved were subjected to sequential probing dilating with an increasing diameter probe repeated in failed cases second and third times at 1-week interval . RESULTS: Medical treatment was effective in only 60 eyes (3.43%) . Probing and syringing achieved successful results in 790 eyes (100%) aged 1 month to 12 months; 330 eyes (99.40%) aged 12 months to 18 months; 200 eyes (98%) aged 18 months to 24 months; 150 eyes (95.24%) aged 24 months to 36 months; and 158 eyes (89.87%) aged 36 months to 48 months . The cure rate with first probing was 98.10%, second probing was 99.64%, and third probing was 100% . CONCLUSIONS: Our protocol of medical regime and early probing repeated two to three times was very effective in the treatment of nasolacrimal duct obstruction at all ages . A second and third probing was recommended after 1 week of the first probing with successful results if first probing failed.

Gen Dent, 2004 May-Jun, 52(3), 244 - 7
Tongue piercing: case report and ethical overview; Dunn WJ et al.; A case of infection following piercing of the tongue is presented . A dentist allegedly provided local anesthesia to the tongue prior to piercing . To avoid criticism from the first dentist, the patient saw a different dentist to treat the infection . The patient had symptoms of pain, inflammation, purulence, salivary incontinence, and difficulty speaking and swallowing . The ornament was discarded and the infection was resolved with antibiotic therapy . Ethical issues of administering anesthesia prior to piercing also are discussed.

Arch Gynecol Obstet, 2004 May, 269(4), 233 - 6 Epub 2003 Dec 19.
Granulomatous mastitis; Diesing D et al.; INTRODUCTION: Granulomatous mastitis (GM) is a rare disease which predominantly occurs in premenopausal women shortly after their last childbirth . ETIOLOGY: Its etiology is unclear, however, the disease has been shown to be correlated with breast-feeding and the use of oral contraceptives . An autoimmune component has also been discussed . PRESENTATION: It presents with the clinical symptoms of galactorrhea, inflammation, breast mass, tumorous indurations and ulcerations of the skin . In mammography and sonography nodular opacities and hypoechoic nodules are found . Very often clinical and radiological findings mimic breast cancer . HISTOLOGICAL DIAGNOSIS: The diagnosis is made by histopathology . Histological features in GM include signs of a chronic granulomatous inflammation with giant cells, leucocytes, epitheloid cells and macrophages as well as abscesses . TREATMENT: Therapy of GM consists of complete surgical excision combined with oral steroid therapy, eventually in combination with anti-inflammatory drugs or colchicine . Use of methotrexate has also been successful . In case of formation of abscesses antibiotic therapy should be applied before steroid therapy . Immune-suppressive therapy should be performed until complete remission as rates of recurrence can be up to 50%.

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz, 2004 Apr, 47(4), 313 - 22
{1974-2004: the Commission for Hospital Hygiene has been working for 30 years . From the "old" to the "new" guideline}; Exner M et al.; After 2 years of preparation, the Commission for Hospital Hygiene, founded in 1974 by the former German Public Health Service, published the "Guideline for Assessment,Prevention, and Controlling of Nosocomial Infections," which represented an exemplarily complete standard for hospital hygiene . In 1997 within the framework of planning the amendment to the Federal Epidemic Law, a new Commission for Hygiene and Infectious Disease Prevention started work and adapted the guideline to meet today's standards of systematic risk analysis and risk management . The amended Infection Protection Act (Infektionsschutzgesetz, IfSG), which came into force in January 2001, installed the Commission for Hospital Hygiene and Infectious Disease Prevention legally and required it to formulate a guideline to decrease the rate of nosocomial infections, the number of outbreaks, and the dissemination of antibiotic-resistant pathogens in healthcare facilities by establishing standards of modern prevention . This article describes the political importance of nosocomial infections for public health as well as the working basis, the methods, and the latest guidelines of the Commission.

Cytotherapy, 2004, 6(3), 183 - 95
Comparison of automated culture systems with a CFR/USP-compliant method for sterility testing of cell-therapy products; Khuu HM et al.; BACKGROUND: Although widely used, commercially available automated culture methods are not US Food and Drug Administration-approved for sterility testing of cell-therapy products . For cell-therapy products regulated under Section 351 of the Public Health Service Act, sterility testing must be performed by the methods described in 21 CFR 610.12 and USP <71> (CFR/USP method), or by methods demonstrated to be equivalent . METHODS: Two automated methods, BacT/Alert (BTA; bioMerieux) and Bactec (Becton Dickinson), were compared with the CFR/USP method . Representative mononuclear cell (MNC) products were formulated using six different product media . MNC product aliquots containing 10-50 x 10(6) cells in a 0.5 mL volume were seeded with organisms, and cultured for 14 days in aerobic and anaerobic bottles of each system . Ten different organisms at target concentrations of 10 and 50 colony-forming units (CFU) per bottle were tested . RESULTS: Positives were detected in a mean (range) of 72% (7-100%) of cultures for CFR/USP, 82% (0-100%) for BTA, and 93% (57-100%) for Bactec . For nine of the 10 organisms tested, overall detection rates for BTA and Bactec were equivalent to or higher than CFR/USP . Of the six product media tested, detection of organisms was impaired only by the medium containing multiple antibiotics: this occurred in all three systems . Both BTA and Bactec had shorter times to detection than the CFR/USP method, with overall means (ranges) of 87 (24-264) h for CFR/USP, 24 (12-54) h for BTA, and 33 (12-80) h for Bactec . Detection occurred consistently within 7 days for both BTA and Bactec, but not for CFR/USP . DISCUSSION: Both BTA and Bactec are superior to the CFR/USP method for overall detection and time to detection of organisms in MNC products suspended in commonly used media . These data support general use of either BTA or Bactec for sterility testing of a variety of cell-therapy products, and suggest that a 7-day culture period is sufficient to detect clinically relevant organisms . These results confirm the need for bacteriostasis and fungistasis testing of antibiotic-containing products, even when antibiotic-binding substances are used.

J Org Chem, 2004 Jun 25, 69(13), 4446 - 53
Synthesis and conformational analysis of 1-{2,4-dideoxy-4-C-hydroxymethyl-alpha-l-lyxopyranosyl}thymine; Vanheusden V et al.; Previously different types of nucleosides with a six-membered carbohydrate moiety have been evaluated for their potential antiviral and antibiotic properties and as building blocks in nucleic acid synthesis . However, a pyranose nucleoside with a 1,4-substitution pattern like 1-{2,4-dideoxy-4-C-hydroxymethyl-alpha-l-lyxopyranosyl}thymine (4) has not been studied yet . Modeling suggested that this nucleoside would show the (4)C(1) conformation in contrast to anhydrohexitol nucleosides (1) whose most stable conformation is (1)C(4) . The key to the synthesis of 4 involves the stereoselective introduction of the hydroxymethyl group onto the C-4 carbon of the pyranose sugar . Attempts to achieve this via hydroboration/oxidation of a C-4'-exocyclic vinylic intermediate selectively yielded the undesired alpha-directed hydroxymethyl group . Therefore, we envisaged another approach in which the C-4 substituent was introduced upon treatment of 2,3-O-isopropylidene-1-O-methyl-4-O-phenoxythiocarbonyl-alpha-l-lyxopyranose with beta-tributylstannyl styrene . This allowed stereoselective beta-directed introduction of a 2-phenylethenyl group at C-4, which was converted via oxidation/reduction (OsO(4), NaIO(4)/NaBH(4)) into the desired 4-hydroxymethyl group (20) . The resulting 1-O-methyl-2,3,6-tri-O-acetyl-protected sugar was coupled with silylated thymine, using SnCl(2) as Lewis acid (22) . After suitable protection, Barton deoxygenation of the 2'-hydroxyl function of the obtained ribo-nucleoside yielded the desired 2'-deoxynucleoside 4, indeed showing the expected equatorial orientation of the thymine ring ((4)C(1)).

Neurosurg Focus . 2004 Jun 15;16(6):ECP1.
Iatrogenic spondylodiscitis . Case report and review of literature; Tasdemiroglu E et al.; Iatrogenic intervertebral disc space infection is encountered following microsurgical discectomy, percutaneous laser disc decompression, automated percutaneous lumbar nucleotomy operations, and discography . The purpose of this paper is to present a case report and review the literature on the uncommon origins of pyogenic spondylodiscitis and to emphasize the significance of prophylactic antibiotic therapy following transrectal ultrasonography-guided needle biopsy of the prostate (TUGNBP) . According to the authors, this is the first reported case of pyogenic spondylodiscitis as a complication of TUGNBP in the English language literature.

Rev Esp Quimioter, 2004 Mar, 17(1), 57 - 63
{Levofloxacin in patients in the ICU . Factors influencing the choice of dose and its use in combined therapy}; Alvarez Lerma F et al.; This study aimed to identify factors that influence the selection of different approaches to prescribing levofloxacin (e.g., monotherapy vs . combined therapy, 12-h vs . 24-h interval) and the effect on mortality in the ICU . An observational, prospective, multicenter study was conducted . A logistic regression analysis was performed to identify factors associated with the prescription of levofloxacin in combined therapy and at a dose of 500 mg every 12 hours . In addition, a logistic regression analysis was conducted to determine the impact of the different prescribing methods on mortality in the ICU . The most frequently administered initial dose was 500 mg/24 h (48.5%) and 500 mg/12 h (48.3%) . No factors were found to influence the choice of daily dose . A total of 49.7% of levofloxacin prescriptions were in combined therapy . Factors influencing the decision to prescribe a combined regimen included diagnosis of extra-ICU nosocomial infection (OR: 1.97; 95% CI: 1.13-3.42); severe sepsis (OR: 2.56; 95% CI: 1.66-3.94); septic shock (OR: 6.22; 95% CI: 3.54-10.9); and identification of the causative pathogen (OR: 1.99: 95% CI: 1.34-2.95) . The mortality rate was 21.4% and the related factors were septic shock (OR: 3.09; 95% CI: 1.38-6.91); treatment failure (OR: 23.4; 95% CI: 12.3-44.6); and combined therapy (OR: 2.36; 95% CI: 1.21-4.59) . The selection of the initial dose of levofloxacin was not influenced by any factor, as long as the antibiotic was given in combined therapy in patients in whom the cause of the infection had been identified, in patients with greater systemic response, and in nosocomial infection outside the ICU . The selection of combined therapy was associated with a worse prognosis.

Obstet Gynecol Clin North Am, 2004 Jun, 31(2), 429 - 59, viii
Cardiac disease in pregnancy; Klein LL et al.; This article reviews the complications, management and prognosis of cardiac disease in pregnancy.

Zhonghua Liu Xing Bing Xue Za Zhi, 2004 Mar, 25(3), 261 - 4
{A case-control study on risk factors of hypospadias}; Wang JP et al.; OBJECTIVE: Hypospadias is one of the most commonly seen urogenital congenital malformations in males and to identify its etiological factors . METHODS: A hospital-based case-control study was conducted, with 107 hypospadias cases . Two matched controls per case were randomly selected . Both cases and controls were face to face interviewed with a uniformed questionnaire . Conditional logistic regression model was used for univariable and multivariate analysis on SAS 6.12 to estimate odds ratios (OR) and 95 per cent confidence internals (95% CI) . RESULTS: Data from multiple conditional logistic regression analysis showed that hypospadias was positively associated with maternal history of spontaneous abortion (OR = 3.87, 95% CI: 1.60 - 9.39), with threatened abortion in the first or second trimester (OR = 3.57, 95% CI: 1.31 - 9.64), with common cold accompanied fever in the first trimester (OR = 7.63, 95% CI: 2.50 - 23.24), with maternal drug (antibiotic, analgesiscs) exposure during the second trimester (OR = 16.46, 95% CI: 3.46 - 78.21), with paternal exposure to pesticides occupationally (OR = 3.70,95% CI: 1.49 - 9.16), with neonatal low birth weight (OR = 12.62, 95% CI: 2.97 - 53.67), but was negatively associated with maternal diet supplemented with protein in the first trimester (OR = 0.33, 95% CI: 0.15 - 0.74) . CONCLUSIONS: The risk factors of hypospadias seemed to include maternal history of spontaneous abortion, threatened abortion in the first or second trimester, maternal common cold accompanied fever in the first trimester, maternal drug exposure during the second trimester, paternal occupational exposure to pesticides, neonatal low birth weight . However, maternal diet supplemented with protein probably acted as the protective factor for neonatal hypospadias in the first trimester.

Ir Med J, 2004 Apr, 97(4), 108 - 10
Managing exacerbations of COPD: room for improvement; Butler MW et al.; Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a major cause of hospital admissions . Because of the consequent morbidity, mortality and burden on hospital resources, COPD management guidelines have been formulated . We reviewed 62 consecutive patients with AECOPD admitted from September 1st to December 18th 2000 in St . Vincents University Hospital, Ireland, including 3 months follow-up data, to evaluate the quality of care and in particular to assess the care of such patients by respiratory and non-respiratory physicians . There was a frequent failure to objectively confirm the diagnosis of COPD by spirometry (completed in 39 of the 51 patients who, at admission, had been previously labelled with COPD (76%), and in 53 out of 62 patients (85%) at the end of the study period), or to estimate severity by quantifying the FEV1 as a percentage of the normal predicted range (estimated in only 21 of the 39 patients who had spirometry previously performed (53%)) . Those patients managed with input from respiratory physicians were more likely to have their diagnosis of COPD confirmed with spirometry (p < 0.05) . They were also more likely to have out-patient follow-up arranged at discharge (p < 0.05) . There was a trend towards the more frequent prescribing of oxygen to hypoxic patients in "respiratory" than in "non-respiratory" managed cases (p = 0.182) and a shorter hospital stay (0.1 < p < 0.5) . 4 out of 11 severely hypoxaemic patients at admission (PO2 < 7.3kPa) were not screened at discharge for possible long term oxygen therapy (36%) . 20 patients received combination antibiotic therapy with no infiltrate on CXR (32%) . Pulmonary rehabilitation was offered to 12 patients (19%) . 5 out of 18 current smokers had documented smoking cessation advice (28%) and none received smoking cessation pharmacotherapy . Finally we noted that the Hospital In-Patient Enquiry (HIPE) data and casualty department admission books were frequently misleading or medical records unlocatable (in 30 out of 92 cases (33%)) . We conclude that the management of AECOPD at St . Vincent's University Hospital is frequently suboptimal, and may be managed better with respiratory physician involvement . In particular, there could be more frequent spirometric confirmation of the diagnosis of COPD, better screening for long term oxygen therapy and more conservative use of antibiotics . Audit is complicated by difficulty accessing relevant data.

Immunol Rev, 2004 Apr, 198, 267 - 84
Metabolic reprogramming in plant innate immunity: the contributions of phenylpropanoid and oxylipin pathways; La Camera S et al.; In their environment, plants interact with a multitude of living organisms and have to cope with a large variety of aggressions of biotic or abiotic origin . To survive, plants have acquired, during evolution, complex mechanisms to detect their aggressors and defend themselves . Receptors and signaling pathways that are involved in such interactions with the environment are just beginning to be uncovered . What has been known for several decades is the extraordinary variety of chemical compounds the plants are capable to synthesize, and many of these products are implicated in defense responses . The number of natural products occurring in plants may be estimated in the range of hundreds of thousands, but only a fraction have been fully characterized . Despite the great importance of these metabolites for plant and also for human health, our knowledge about their biosynthetic pathways and functions is still fragmentary . Recent progress has been made particularly for phenylpropanoid and oxylipin metabolism, which are emphasized in this review . Both pathways are involved in plant resistance at several levels: by providing building units of physical barriers against pathogen invasion, by synthesizing an array of antibiotic compounds, and by producing signals implicated in the mounting of plant resistance.

J Biomed Mater Res, 2004 Jul 15, 70B(1), 103 - 5
Release of anthracyclines adsorbed on copper-treated hydroxylapatites; Bacha RA et al.; Anthracyclines are antibiotics widely used for the treatment of leukemia and solid tumors . Perfusion is the standard clinical administration form . Unfortunately, this does not allow treatment of gastric cancers . A new galenic presentation, consisting of anthracyclines adsorbed onto hydroxylapatite granules, has been developed . It was found to be possible to modulate the release of the drug as a function of the pH by using copper(II) ions . At neutral pH, the drug remains on the mineral support, but at pH 3, the drug is released into solution . Further investigations demonstrate that copper-containing hydroxylapatite can retain a determined quantity of antibiotic by surface complexation . This result could contribute to new designs for drug carriers targeted for gastric cancers .

Scand J Infect Dis, 2004, 36(4), 312 - 4
Two case reports: fatal Absidia corymbifera pulmonary tract infection in the first postoperative phase of a lung transplant patient receiving voriconazole prophylaxis, and transient bronchial Absidia corymbifera colonization in a lung transplant patient; Mattner F et al.; Absidia corymbifera is a rare cause of pulmonary tract infection . There exist only 5 case reports predominantly diagnosed in bone marrow transplant patients . Lung transplant patients are at high risk for invasive fungal infections . Due to A . corymbifera as pathogen, known to be voriconazole resistant, a fatal invasive pulmonary mycosis occurred . In the present case voriconazole prophylaxis failed . A second patient showed a transient colonization of the bronchi . To prevent airborne transmitted invasive pulmonary mycosis in the first postoperative period of lung transplantation the patient should be situated in a room ventilated by HEPA-filtered air . The specific treatment should start very early when first suspicion arises . A review of the literature on pulmonary tract infections induced by Absidia corymbifera is provided.

Support Care Cancer, 2004 Aug, 12(8), 555 - 60 Epub 2004 Jun 09.
Febrile neutropenia: a prospective study to validate the Multinational Association of Supportive Care of Cancer (MASCC) risk-index score; Uys A et al.; OBJECTIVE: The objective of this study was to prospectively validate the Multinational Association of Supportive Care of Cancer (MASCC) risk-index score in an attempt to accurately predict on presentation with febrile neutropenia those cancer patients who are at low- or high-risk for development of serious medical complications during the episode . PATIENTS AND METHODS: Patients who presented with febrile neutropenia during November 2000 and July 2002 were prospectively enrolled in the protocol . All patients were hospitalized until recovery or outcome of the event and were treated with broad-spectrum, empiric, intravenous antibiotic therapy . The MASCC risk-index score (based on seven independent factors present at onset of febrile neutropenia) was calculated in 64 patients with 80 febrile neutropenic episodes . Patients with a score of > or =21 were regarded as low risk; patients with a score of <21 were regarded as high risk . RESULTS: Of the 80 febrile neutropenic episodes, 58 were classified as low-risk and 22 as high-risk patients . Fifty-seven (98.3%) of the 58 low-risk patients recovered without complications, and three (13.6%) of the 22 high-risk patients did not develop medical complications . One low-risk patient developed a fungal infection but recovered completely in comparison to 11 high-risk patients (50%) who developed serious medical complications ( p<0.001) . None of the low-risk patients died . However, eight (36.4%) of the 22 high-risk patients died during the febrile neutropenic episode ( p<0.001), six as a consequence of sepsis and two due to rapidly uncontrolled cancer . CONCLUSION: We correctly predicted 98.3% of low-risk patients and 86.3% of high-risk patients . This study had a positive predictive value of 98.3% and a negative predictive value of 86.4% with both a sensitivity and specificity of 95% . The MASCC risk-index score correctly identifies low- and high-risk patients at presentation with febrile neutropenia.

Arch Surg, 2004 Jun, 139(6), 603 - 7; discussion 607-8
Early experience with balloon brachytherapy for breast cancer; Dowlatshahi K et al.; HYPOTHESIS: Partial-breast irradiation for carcinoma by a single source of radiation placed in the center of a balloon inserted in the lumpectomy cavity is an effective method of treating breast cancer . Previous interstitial radiation therapy using iridium seeds placed within multiple catheters has been shown to be effective but impractical and cosmetically unacceptable to women . DESIGN: Prospective registry study . SETTING: Three university and community hospitals . PATIENTS: Women 40 years and older with histologically diagnosed in situ and invasive T1 through T2 and N0 or N1 breast cancer treated with lumpectomy and axillary node sampling were invited to enter this institutional review board-approved study . MAIN OUTCOME MEASURES: Evaluation of immediate and short-term complications, patients' acceptance of the treatment, and cosmesis are reported . RESULTS: Of the 129 eligible patients enrolled, 112 completed the treatment . Of these, transient skin erythema was noted in 28, localized edema in 3, and skin blisters adjacent to the balloon in 9 . Infection developed in 7, necessitating drainage and antibiotic administration . In 10 patients, sonographically demonstrated seromas that developed after removal of the device were aspirated percutaneously . In 4 patients, punctured or ruptured balloons had to be replaced before the treatment could be completed . Patients quickly adjusted to the breast distension caused by the balloon, and their acceptance of the procedure was good . The cosmetic outcome was rated high . There were no recurrences during this very short follow-up . CONCLUSIONS: Our early short-term experience indicates balloon brachytherapy to be an acceptable alternative to external beam radiation for selected operable breast cancers . The 1-week treatment time allows working women and those who live at a distance from radiation centers to choose breast conservation rather than mastectomy.

Crit Care, 2004, 8 Suppl 2, S27 - 30 Epub 2004 Jun 14.
To filter blood or universal leukoreduction: what is the answer?
Shapiro MJ.
The safety of the blood supply has been a concern over the past 20-30 years because of the transmission of infectious diseases . Blood is still routinely tested for viruses, and leukoreduction is an effective strategy to reduce the transmission of cell-associated viruses . Clinically, the benefits of leukoreduction include decreases in transfusion reactions, HLA alloimmunization, infections, fever episodes, and antibiotic use . Although leukoreduction will add cost to a unit of blood, projections indicate that leukoreduced blood will become the standard of care.

Arch Environ Contam Toxicol, 2004 Apr, 46(3), 289 - 95
A procedure to purify and culture a clonal strain of the aquatic moss Fontinalis antipyretica for use as a bioindicator of heavy metals; Rausch de Traubenberg C et al.; A procedure to culture the aquatic moss, Fontinalis antipyretica, is described . The moss was collected in a stream, carried to the laboratory, and immediately treated: apices were isolated and rinsed under a stereomicroscope and submitted to ultrasonic cleaning combined with an iodine treatment and then to an antibiotic/anti-eukaryotic treatment for 4 days . This procedure permitted us for the first time to eliminate the microalgae associated with an aquatic moss in culture, solving the problem of proliferation of these microalgae in the culture medium . Furthermore, the minimal concentration of eight essential metals required by this moss was determined in order to have metal concentrations in the cultured moss as low as possible . A perennial culture of a clonal strain of an aquatic moss for use as a metal bioaccumulator was obtained and the first step to provide a standardized bioindication tool for metal detection in continental waters was passed over.

Zhonghua Er Bi Yan Hou Ke Za Zhi, 2004 Feb, 39(2), 112 - 5
{Effect of specific immunoglobulin Y in the treatment of acute and chronic pharyngitis}; Xie MQ et al.; OBJECTIVE: To evaluate the effect and safety of the specific immunoglobulin Y (IgY) for treatment of acute and chronic pharyngitis . METHODS: Double-blind, randomized, placebo-controlled trial was conducted on 50 adults with acute pharyngitis . Experimental group received a 6 times-daily total 30 doses of IgY stomat-spray which contained specific immunoglobulin Y (titer = 512) prepared from the egg yolk of hens immunized with a variety of bacteria . Another open label trial included 50 patients, whose ages ranged from 21-69 years, including 25 cases of acute pharyngitis and 25 cases of chronic pharyngitis were also treated using IgY stomat-spray . The therapeutic effect were objectively evaluated 7 days later by the decreased scores based on both the symptoms and physical signs . If the symptom did not improve or became severe three days later, these patients with acute pharyngitis was inefficiency and antibiotic medicine would be added to them . RESULTS: In Double-blind trial, 8 cases (32%) received IgY had apparent effect with the decreased scores 5 or more than 5, 13 cases (52%) had effective with the decreased scores 3-4, and other 4 cases (16%) had inefficacy with the decreased scores only 2 or no more than 2 . While in placebo-controlled group, only 2 (8%) cases had apparent effect, 5 (20%) cases showed effective and 18 (72%) cases had non-effect . The difference between the two groups was significant (chi 2 = 16.06, P < 0.01) . In open label trial, 19 cases (38%) showed apparent effect, in which 14 cases were acute pharygitis . 23 cases (46%) had effective, in which 10 cases were acute pharyngitis . The left 8 cases (16%) had ineffective, in which one case was acute pharyngitis . There was significantly difference (chi 2 = 8.90, P < 0.05) between acute pharyngitis and chronic pharyngitis . An average of three months followup showed that there were no side effect or toxic effect and no allergic reaction . CONCLUSION: The IgY stomat-spray is a safe and effective agent in treating acute and chronic pharyngitis, especially for acute pharyngitis.

Neuroreport, 2004 Jun 28, 15(9), 1379 - 82
Medial olivocochlear efferent activity in awake guinea pigs; Guitton MJ et al.; Cochlear outer hair cells receive numerous connections from the medial olivocochlear efferent neurons . Medial olivocochlear efferent activity is highly dependent on the level of anesthesia . The present study was thus designed to investigate the efficiency of contralateral white noise stimulation on the distortion product otoacoustic emissions (DPOAEs) in a large number of awake guinea pigs, and to compare in the same animals the effect of urethane- and pentobarbitone-anesthesia . The monitoring of DPOAEs during contralateral white noise stimulation in awake animals requires the development of a soft restraining box, together with a conditioning technique for the animals to accept the contralateral sound and DPOAEs monitoring device . This technique allows us to demonstrate that contralateral sound suppression is much stronger in awake than in anesthetized animals . In all the cases, the contralateral sound suppression was abolished 3 h after i.m . injection of gentamicin, an aminoglycoside antibiotic which blocks the medial olivocochlear efferents . These results suggest that future studies have to explore the function of medial olivocochlear efferents in awake animals.

Pediatr Infect Dis J, 2004 Jun, 23(6), 590 - 1
Mycobacterium bovis versus Mycobacterium tuberculosis as a cause of acute cervical lymphadenitis without pulmonary disease; Fennelly GJ; Bovine tuberculosis remains a common disease of cattle in countries such as Mexico . Children eating unpasteurized dairy products from Mexican cattle can develop Mycobacterium bovis cervical lymphadenitis . However, the bovine mycobacterium can be misdiagnosed as Mycobacterium tuberculosis based on standard laboratory testing . Accurate speciation is important for selection of the preferred antibiotic regimen for treatment of Mycobacterium bovis infection.

J Am Coll Surg, 2004 Jun, 198(6), 877 - 83
Outcomes and prediction of hospital readmission after intestinal surgery; Kiran RP et al.; BACKGROUND: Clinical care pathways reduce postoperative stay after major bowel operations . Concerns about unexpected early readmissions and delays in diagnosis of complications remain unanswered . The objectives of this study were determination of readmission rate and outcomes for patients undergoing intestinal operations . STUDY DESIGN: Patients readmitted (PR) within 30 days of discharge after intestinal operations were compared with patients who were not readmitted (NR) . Variables that might predict readmission were evaluated . RESULTS: Of 553 patients, 56 (10.1%) were readmitted after 10 days (interquartile range {IQR} 4.5 to 15.5 days) . PR and NR groups had similar age, gender, diagnosis, preoperative comorbidities, and index operations . Discharge hemoglobin level, white cell count, antibiotic use, or presence of stoma did not affect readmission . PR had a greater frequency of steroid use (p = 0.03) during index admission . Median length of stay for the index hospitalization was 5 days (IQR 4 to 8 days) for the NR and 6 days (IQR 4.8 to 9 days) for the PR group (p = 0.049) . Duration of readmission was 4 days (IQR 2 to 9 days) in the PR group, with equal total median length of stay identical for PR and NR patients with complications (median 12 days) . Clinical outcomes for PR patients and NR patients with complications were similar . CONCLUSIONS: Early readmission is an unpredictable sequel of major bowel operations; it does not correlate with shorter hospital stay . Identification of unpredictable complications after discharge that require later invasive intervention does not adversely affect clinical outcomes . Readmission within 30 days of a patient who has attained standardized discharge criteria may not be a valid indicator of poor quality of care.

Med Hypotheses, 2004, 63(1), 31 - 4
Why minocycline can cause systemic lupus - a hypothesis and suggestions for therapeutic interventions based on it; van Steensel MA; The tetracycline antibiotic minocycline is widely used in dermatology, but can sometimes cause systemic lupus erythematodes, a serious autoimmune disorder . It is not known how it does this . However, recent data suggest that minocycline can protect cells from apoptosis by inhibition of caspase-dependent and independent cell death pathways . Here, it is suggested that this ability of minocycline is responsible for the induction of lupus . This idea is based on the recent insight that incomplete or failed apoptosis of damaged cells, particularly keratinocytes, may be responsible for the development of auto-immunity . The protection against apoptosis as conferred by minocyclin may be incomplete, with failed apoptosis and development of autoimmunity as a result . Experimental confirmation of the theory may be obtained by in vitro experiments using induction of apoptosis in cell types known to be affected by lupus . Next, mice that are sensitive to apoptosis may be used for in vivo experiments . Novel therapeutic approaches to drug-induced lupus may be based on induction of apoptosis; DNA-damaging immunosuppressive agents appear particularly useful . Such treatments can be tested in apoptosis-deficient mice that develop autoimmune disease.

Apoptosis, 2004 Jul, 9(4), 429 - 35
Characterization of 4-O-methyl-ascochlorin-induced apoptosis in comparison with typical apoptotic inducers in human leukemia cell lines; Tsuruga M et al.; Apoptosis can be induced by various stimuli such as the ligands of death receptors, chemotherapeutic drugs and irradiation . It is generally believed that chemotherapeutic drugs induce mitochondrial damage, cytochrome c release and activation of caspase-9, leading to apoptosis . Here, we found that an isoprenoid antibiotic, 4-O-methyl ascochlorin, significantly induces typical apoptotic events in Jurkat cells including the degradation of poly (ADP-ribose) polymerase, DNA fragmentation, activation of caspase-3, -9 and -8, and cytochrome c release from mitochondria . Similar to Fas stimulation, 4-O-methyl ascochlorin but not staurosporine, cycloheximide and actinomycin D, induced apoptosis in SKW6.4 cells, in which apoptosis is strongly dependent on death-inducing signaling-complex . Bcl-2 overexpression in Jurkat cells completely suppressed the apoptosis, but procaspase-9 processing was partially induced . A caspase-8 inhibitor, IETD-fmk, effectively suppressed poly (ADP-ribose) polymerase cleavage and cytochrome c release . However, 4-O-methyl ascochlorin induced apoptosis in Jurkat cells deficient of caspase-8 or Fas-associated death domain protein . These results suggest that 4-O-methyl ascochlorin induces apoptosis through the mechanism distinct from conventional apoptosis inducers .

Adv Ther, 2004 Jan-Feb, 21(1), 39 - 46
Serum IL-8 as a possible marker for determining the status of Helicobacter pylori infection in patients with untreated and treated peptic ulcer; Cheng KS et al.; Failure to eradicate Helicobacter pylori can lead to peptic ulcer recurrence and gastric malignancy . Therefore, the objective of this study was to develop a noninvasive method for determining whether H . pylori infection was eradicated with antibiotic-based triple therapy . A total of 17 patients with duodenal ulcer (DU) and 17 with gastric ulcer (GU) were evaluated both before and after treatment . Outcomes included serum levels of interleukin-8 (IL-8), pepsinogen I, and gastrin, and the Wilcoxon signed rank test was used to test significance . Changes in these parameters were also correlated with disease status . In those patients where both GU and DU healing occurred as a result of treatment, most showed an increase in serum IL-8 and a decrease in serum pepsinogen . Serum gastrin levels were not significantly changed in either group . Posttreatment increases in serum IL-8 were seen in 15 of 17 (88%) recovered DU patients and 14 of 17 (82%) recovered GU patients (P<.05 for each) . Posttreatment decreases in pepsinogen I were found in 15 of 17 DU and 15 of 17 GU patients (P<.05 for each) . These preliminary findings suggest that an increase in serum IL-8 and possibly a decrease in pepsinogen I may be useful in identifying the successful eradication of H . pylori infection in patients with peptic ulcer treated with antibiotics . A more systematic analysis of these putative diagnostic markers is now warranted.

J Healthc Manag, 2004 May-Jun, 49(3), 199 - 205
Getting a return on investment from spending capital dollars on new beds; Hardy PA; In assessing this bed-purchase process and the resulting return on investment, I identified the following critical success factors related to capital investments: Evaluation of capital equipment for return on investment from the expense side, particularly when looking at use of manpower for critical positions in the organization Evaluation of capital equipment for increasing nursing satisfaction, a factor in addressing the healthcare worker shortage in today's environment Involvement of a representative team to create personal ownership through individuals wanting to take care of something they are involved in purchasing Spin-off timesaving that can be realized through the adage "form follows function" The last factor was found not only in savings of nurse staff time but also in pharmacy time because the weight function on the new beds saved approximately one hour, allowing for speedier calculation of creatinine clearance in antibiotic dosing . Changing my position and perspective was rewarding . The persistence of the CNO and the involvement of the employees made the experience gratifying on a personal level as well.

Harefuah, 2004 May, 143(5), 377 - 81, 389
{An update on probiotics and prebiotics in children}; Shaoul R et al.; This review presents an update on the use of probiotics and prebiotics in children . We review the normal flora, and present the possible mechanisms by which the probiotic bacteria exert their beneficial effects . We present data from multiple studies suggesting that probiotics are effective for the treatment and prevention of acute non-bloody infections diarrhea, antibiotic associated diarrhea as well as the prevention and treatment of atopic dermatitis and other allergic conditions . The safety and future directions of pro- and prebiotic treatments are discussed.

J Health Popul Nutr, 2004 Mar, 22(1), 46 - 51
Management of childhood febrile illness prior to clinic attendance in urban Nigeria; Afolabi BM et al.; Parents and caregivers often try various treatment modalities for their sick children before bringing them to clinic . Many community-based studies have documented home and self-treatment practices, often with the aid of patent medicine vendors, but less is known about prior treatment behaviour of caregivers who actually reach a government clinic . This study, therefore, aimed at documenting the treatment provided by caregivers prior to their attendance at a public hospital . Beginning in April 1996, a year-long study was conducted among 1,943 sick children and their caregivers who attended the largest government-owned paediatric hospital in Lagos, Nigeria . The major complaints mentioned by the caregivers included fever, cough, and diarrhoea . Most (89%) caregivers had administered some form of medicine to the child prior to the clinic visit, and on average, 2.5 medications had been given . Associations were found between major complaint and type of medicine given: fevers were associated with antimalarial drugs and analgesics (antipyretics), cough was associated with cough syrup and analgesics, while diarrhoea was associated with antidiarrhoeal drugs . Although one-fifth of the children had received an antibiotic, provision of antibiotics was not associated with a particular complaint/illness . Since caregivers appeared to use perceived complaints/illnesses as a treatment guide, this can form the basis of safer and more appropriate recognition of illness and home management . In addition, the information obtained in this study can be used for training clinicians to inquire about home management and, thus, for making more informed decisions about their own treatment and prescribing practices.

Hua Xi Kou Qiang Yi Xue Za Zhi, 2004 Apr, 22(2), 96 - 9
{Transfection of human endostatin gene with lipofectamin and the expression of hES protein in Tca8113 cell}; Pan CB et al.; OBJECTIVE: The purpose of this study was to establish transfergeneic Tca8113 cell and evaluate the expression of human endostatin (hES) gene in the cell colone in vitro . METHODS: To transfect hES gene into Tca8113 cells, lipofectamin was complexed with plasmid encoding hES gene, and blasticidin S antibiotic was adopted to select Tca8113--hES cell clone . Immunohistochemistry S-P method was adopted to detect the expression of hES in the transfergenic Tca8113 cell in vitro . RESULTS: Transfected by hES, the transfergenic Tca8113 cells could grow and proliferate in RPMI--1640 culture medium containing blasticidin S antibiotic . The expression rate of hES reached 100% . CONCLUSION: hES gene can express in hES-transfected Tca8113 cell in vitro.

Rev Port Pneumol, 2003 Nov-Dec, 9(6), 503 - 14
{Difficulties on diagnosis of ventilator associated pneumonia}; Machado MA et al.; Ventilator associated pneumonia is associated with high morbidity and mortality . It is important a correct diagnosis in way to guide the antibiotic therapy in the most appropriate way . However, its diagnosis is difficult, because clinical and radiologic features are not specific and approaches to standard diagnosis, that allow its confirmation, are very invasive or not very frequent . Protected techniques and quantitative cultures have been trying to outline the problem of the contamination of the samples obtained by routine methods and to allow the distinction between colonization and infection . The author makes a revision on the different methods of diagnosis of this clinical entity.

Biophys J, 2004 Jun, 86(6), 3687 - 99
Peptaibol zervamicin IIb structure and dynamics refinement from transhydrogen bond J couplings; Shenkarev ZO et al.; Zervamicin IIB (Zrv-IIB) is a channel-forming peptaibol antibiotic of fungal origin . The measured transhydrogen bond (3h)J(NC') couplings in methanol solution heaving average value of -0.41 Hz indicate that the stability of the Zrv-IIB helix in this milieu is comparable to the stability of helices in globular proteins . The N-terminus of the peptide forms an alpha-helix, whereas 3(10)-helical hydrogen bonds stabilize the C-terminus . However, two weak transhydrogen bond peaks are observed in a long-range HNCO spectrum for HN Aib(12) . Energy calculations using the Empirical Conformation Energy Program for Peptides (ECEPP)/2 force field and the implicit solvent model show that the middle of the peptide helix accommodates a bifurcated hydrogen bond that is simultaneously formed between HN Aib(12) and CO Leu(8) and CO Aib(9) . Several lowered (3h)J(NC') on a polar face of the helix correlate with the conformational exchange process observed earlier and imply dynamic distortions of a hydrogen bond pattern with the predominant population of a properly folded helical structure . The refined structure of Zrv-IIB on the basis of the observed hydrogen bond pattern has a small ( approximately 20 degrees ) angle of helix bending that is virtually identical to the angle of bending in dodecylphosphocholine (DPC) micelles, indicating the stability of a hinge region in different environments . NMR parameters ((1)HN chemical shifts and transpeptide bond (1)J(NC') couplings) sensitive to hydrogen bonding along with the solvent accessible surface area of carbonyl oxygens indicate a large polar patch on the convex side of the helix formed by three exposed backbone carbonyls of Aib(7), Aib(9), and Hyp(10) and polar side chains of Hyp(10), Gln(11), and Hyp(13) . The unique structural features, high helix stability and the enhanced polar patch, set apart Zrv-IIB from other peptaibols (for example, alamethicin) and possibly underlie its biological and physiological properties.

Infection, 2004 Jun, 32(3), 176 - 8
Trimethoprim-sulfamethoxazole exacerbates posthypoxic action myoclonus in a patient with suspicion of Pneumocystis jiroveci infection; Jundt F et al.; We describe a 58-year-old patient with relapsing high-grade non-Hodgkin's lymphoma who exhibited exacerbation of posthypoxic action myoclonus during high-dose intravenous trimethoprim-sulfamethoxazole (TMP-SMX) treatment for highly suspicious Pneumocystis jiroveci pneumonia (PCP) . Three months previously the patient had experienced a hypoxic insult caused by respiratory arrest due to an anaphylactic reaction to antibiotic therapy . He had developed posthypoxic action myoclonus (Lance-Adams syndrome), which was well controlled by oral treatment with piracetam . However, after TMP-SMX therapy (115 mg/kg daily) was started for suspicion of newly developed PCP, posthypoxic action myoclonus worsened dramatically resulting in complete disability . Anti-myoclonic therapy with increased doses of piracetam and valproic acid did not significantly improve his clinical condition . Only when TMPSMX doses were reduced (38 mg/kg daily) on day 12 did action myoclonus cease within 2 to 3 days . We suggest that TMP-SMX can exacerbate posthypoxic action myoclonus . Copyright Urban and Vogel

An Otorrinolaringol Ibero Am, 2004, 31(2), 105 - 13
{Latero-pharyngeal phlegmons and abscesses in adults . Reports of 6 cases and literature review}; Pino Rivero V et al.; Lateropharyngeal phlegmons and abscesses are an uncommon complication actually but they are requiring an adequate knowledge to get later an adequate treatment . We are reporting a clinical review of 6 cases corresponding to adults admitted by our ENT service in 11 years period . Four were men and two women with ages between 21 and 92 years old . In most of them it was found a pharyngotonsillar focus and after the diagnosis they were treated by endovenous antibiotic therapy, corticoid and, in one case, surgery by incision and drainage . All the patients had a satisfactory evolution standing between 6-12 days in the hospital . We have performed a bibliographic review on this subject.

Akush Ginekol (Sofiia), 2004, 43(2), 11 - 3
{Immunostimulation as a part of urologic infection therapy in pregnancy}; Nikolov A et al.; Twenty-six pregnant women (group I) with uroinfection were treated with Urostim and antibiotic . The effect of treatment was compared to that of 20 pregnant women (group II) treated with antibiotic only . In group I recurrence of infections was found out in 15.3%, while in group II in 55% . We would like to offer it as part of the treatment of uroinfections with pregnant women, because it will reduce the usage of antibiotics and the recurrence of the uroinfections in postpartum period.

J Pediatr Surg, 2004 Jun, 39(6), 875 - 9; discussion 875-9
The management of pediatric appendicitis: a survey of North American Pediatric Surgeons; Muehlstedt SG et al.; BACKGROUND/PURPOSE: Variation exists among pediatric surgeons in the management of pediatric appendicitis . The goal of this study was to determine current practice patterns and provide a foundation for evidence-based outcome studies that would standardize patient care . METHODS: Members of the American Pediatric Surgical Association (APSA) were surveyed . Data included preference of imaging, timing of operation, and opinions on interval appendectomy . Intraoperative principles surveyed included use of cultures, antibiotic irrigation, transperitoneal drains, and method of wound closure . Spectrum and duration of antibiotic coverage were assessed, as were discharge criteria . RESULTS: Survey response was 70% . A majority prefers computerized tomographic (CT) imaging and favors interval appendectomy in appropriate candidates . Seventy percent indicate a stable child with suspected appendicitis would be operated on in a semiurgent manner rather than emergently in their practice . Discrepancy exists in the type and duration of antibiotic coverage, impact of clinical parameters on antibiotic use, and utility of discharge criteria . CONCLUSIONS: This study consolidates current opinions on appropriate management of pediatric appendicitis, providing a foundation for evidence-based outcome studies capable of bringing conformity to the management of this surgical disease . Such studies would establish clinical practice guidelines that optimize resource utilization while maintaining quality care.

Appl Environ Microbiol, 2004 Jun, 70(6), 3733 - 5
Methods for enhanced culture recovery of Francisella tularensis; Petersen JM et al.; Francisella tularensis is found in a wide variety of hosts and extrahost environments, making culture recovery a diagnostic challenge . Here we demonstrate improved recovery times and good sensitivity (90%) when cultures were inoculated on the site of an investigation using fresh tissues . For contaminated specimens, antibiotic supplementation of enriched cysteine heart agar blood culture medium improved recovery of F . tularensis by 81.1% . For transport of tissues, immediate freezing yielded culture recovery rates as high as 94%.

Urology, 2004 Jun, 63(6), 1182 - 3
Eosinophilic cystitis after bladder instillation with dimethyl sulfoxide; Abramov Y et al.; Eosinophilic cystitis is a rare and poorly understood disorder . We report the first case of an acute flare of eosinophilic cystitis in a 51-year-old woman after bladder instillation with dimethyl sulfoxide (DMSO) for presumed interstitial cystitis . The patient presented with severe bladder pain, fever, and eosinophilia several hours after instillation . These symptoms were unresponsive to conventional analgesic and antibiotic treatments . Cystoscopy revealed erythema and exudate at the bladder walls, along with edema of both ureteral orifices . Bladder biopsies demonstrated massive eosinophilic infiltration of the bladder, confirming the diagnosis of eosinophilic cystitis . Urologists should bear in mind this clinical entity, particularly when DMSO is administered to patients with multiple drug allergies.

Urology, 2004 Jun, 63(6), 1017 - 20; discussion 1020
Three-dimensional ultrasound guidance for percutaneous drainage of prostatic abscesses; Varkarakis J et al.; OBJECTIVES: To evaluate the feasibility and effectiveness of three-dimensional ultrasound-guided transperineal puncture and drainage of prostatic abscesses . METHODS: Between 1985 and 2003, a prostatic abscess was diagnosed in 22 patients . One of the therapeutic modalities used to drain the abscesses was transperineal puncture under three-dimensional ultrasound guidance . The postoperative results were compared with the outcomes of other modalities . RESULTS: The average patient age was 52 years . Predisposing factors were present in 12 patients . Transperineal puncture was performed in 7 patients under general anesthesia . In addition to antibiotic therapy, a nephrostomy tube was left in place in all cases for a mean period of 3 days to drain the abscess . All patients were treated effectively without additional therapy or complications . CONCLUSIONS: Three-dimensional ultrasound-guided transperineal puncture is a minimally invasive and effective technique for the treatment of prostatic abscesses.

Biomed Pharmacother, 2004 May, 58(4), 239 - 44
Artificial neural network modeling to predict the plasma concentration of aminoglycosides in burn patients; Yamamura S et al.; The goal was to use an artificial neural network model to predict the plasma concentration of aminoglycosides in burn patients and identify patients whose plasma antibiotic concentration would be sub-therapeutic based on the patients' physiological data and taking into account burn severity . Physiological data and some indicators of burn severity were collected from 30 burn patients who received arbekacin . A three-layer artificial neural network with five neurons in the hidden layer was used to predict the plasma concentration of arbekacin . Linear modeling for prediction of plasma concentration and logistic regression modeling for the classification of patients were also used and the predictive performance was compared to results from the artificial neural network model . Dose, body mass index, serum creatinine concentration and amount of parenteral fluid were selected as covariates for the plasma concentration of arbekacin . Area of burn after skin graft was a good covariate for indicating burn severity . Predictive performance of the artificial neural network model including burn severity was much better than linear modeling and logistic regression analysis . An artificial neural network model should be helpful for the prediction of plasma concentration using patients' physiological data, and burn severity should be included for improved prediction in burn patients . Because the relationship between burn severity and plasma concentration of aminoglycosides is thought to be nonlinear, it is not surprising that the artificial neural network model showed better predictive performance compared to the linear or logistic regression models.

Can J Urol, 2004 Apr, 11(2), 2210 - 5
Posterior urethral valves in Eastern Ontario - a 30 year perspective; Warren J et al.; INTRODUCTION: Posterior urethral valves (PUV) are the most common cause of male pediatric obstructive uropathy . Recent advancements in antenatal ultrasound and endoscopy have altered the presentation and management of PUV . Herein we describe the presentation, management and outcome of PUV patients in Eastern Ontario/Western Quebec over the last 3 decades . A comparison analysis of those cases identified pre and post widespread utilization of antenatal ultrasound diagnosis was performed to discern the clinical evolution of PUV with respect to long-term outcome . METHODS: Retrospective systematic chart review of all PUV cases diagnosed and treated at the Children's Hospital of Eastern Ontario over the last 3 decades . Charts were reviewed for initial presentation, method of diagnosis, radiological and clinical findings at diagnosis, initial management, and long-term clinical outcome . The evolution of PUV was interpreted by dividing the cohort into two groups chronologically delineated by the first case detected by antenatal ultrasound in the mid-1980s . These pre- and post- antenatal ultrasound eras were compared with respect to the parameters outlined above . RESULTS: Fifty-three cases were reviewed - 21 prior to widespread antenatal ultrasound screening in the mid-1980s and 32 after . There were 13/53 cases (32%) discovered by prenatal ultrasound evidence of hydronephrosis, none prior to 1985 . VCUG confirmed the diagnosis in all cases . Mean age at presentation in the remaining post-natally diagnosed patients was 33 months . Of the cases diagnosed post-natally, ultrasound investigation complemented VCUG findings in 19/40 cases (47%), whereas IVP was utilized in 14/40 (35%) . IVP has not been utilized for this purpose since 1987 . Overall, 26/53 cases (49%) had documented VUR - 16/26 (62%) bilateral; 42/53 (79%) had hydronephrosis on ultrasound - 37/42 (88%) bilateral; 26/53 (49%) had radiological evidence of renal parenchymal damage at diagnosis; 41/53 (77%) cases had a thickened bladder wall on ultrasound at diagnosis, and 23/53 (43%) had at least one bladder diverticulum . Techniques of initial management comprised: valve ablation 32/53, vesicostomy 11/53, and high diversion 10/53 . Clinically significant bladder dysfunction was found in 31% of cases, ranging from bladder instability to myogenic failure . Globally impaired renal function, as determined by significantly elevated serum creatinine levels, reduced GFR, or both, was found in 12/53 (23%) . 6/53 (11%) progressed to ESRD, of which 4 received transplants . Two patients died - one from complications related to renal failure . Of the six cases of myogenic bladder failure identified, three (50%) had concurrently significant renal impairment . Average length of follow-up was 8.3 years, varying between 1 month and 18 years . CONCLUSIONS: The presentation of PUV is variable, and currently antenatal detection is the most common mode . Despite this, it still does not make up the majority of diagnoses . Complete radiological work up should include abdominal and pelvic U/S in conjunction with VCUG . Concurrent VUR in 50% of boys mandates suppressive antibiotic use . Primary valve ablation remains the gold standard for treatment of PUV, with vesicostomy reserved for selected cases . Long-term bladder and renal dysfunction is common in this population, and mandates long-term urological and nephrological follow-up.

Cutis, 2004 May, 73(5 Suppl), 23 - 4
The dermatologist's role in managing skin and soft tissue infections; Zalar GL; Dermatologists are often the first point of care for patients with skin and soft tissue bacterial infections . First, physical examination and patient history are central points of assessment to determine severity of infection, pathogen involved, and appropriate course of action . As preexisting conditions may exert a role both in the etiology of an infection and in the choice of antibiotic therapy prescribed, the clinician must be aware of the right questions to ask to achieve a complete diagnostic picture . Finally, the clinician should have a good understanding of the drugs most appropriate for different pathogens and have clear expectations of how quickly the infection should respond to therapy.

Arch Pharm Res, 2004 Apr, 27(4), 407 - 14
Histone deacetylase inhibitor stimulate CYP3A4 proximal promoter activity in HepG2 cells; Kim JY et al.; The expression of CYP3A4 gene is induced by a variety of structurally unrelated xenobiotics including the antibiotic rifampicin, pregnenolone 16-carbonitrile (PCN), and endogenous hormones, that might mediate through steroid and xenobiotic receptor (SXR) system . The molecular mechanisms underlying regulation of CYP3A4 gene expression have not been understood . In order to gain the insight of the molecular mechanism of CYP3A4 gene expression, study has been undertaken to investigate if the histone deacetylation is involved in the regulation of CYP3A4 gene expression by proximal promoter in human hepatoma HepG2 cells . Also we have investigated to see if SXR is involved in the regulation of CYP3A4 proximal promoter activity in human hepatoma HepG2 cells . HepG2 cells were transfected with a plasmid pCYP3A4-Luc containing approximately 1 kb of the CYP3A4 proximal promoter region (-863 to +64 bp) in front of a reporter gene, luciferase, in the presence or absence of pSAP-SXR . In HepG2 cells, CYP3A4 inducers, such as rifampicin, PCN and RU486 showed minimal stimulation of CYP3A4 proximal promoter activity in the absence of SXR and histone deacetylase (HDAC) inhibitors . 4-Dimethylamino-N-{4-(2-hydroxycarbamoylvinyl)benzyl}benzamide (IN2001), a new class HDAC inhibitor significantly increased CYP3A4 proximal promoter activity over untreated control cells and rifampicin concomitant treatment with IN2001 increased further CYP3A4 proximal promoter activity that was stimulated by IN2001 . The results of this study demonstrated that both HDAC inhibitors and SXR are essential to increase of CYP3A4 proximal promoter activity by CYP3A4 inducers such as PCN, rifampicin, and RU486 . Especially SXR seems to be important for the dose dependent response of CYP3A4 inducing chemicals to stimulate CYP3A4 proximal promoter activity . Also this data suggested that HDAC inhibitors seemed to facilitate the CYP3A4 proximal promoter to be activated by chemicals.

Osaka City Med J, 2003 Dec, 49(2), 57 - 60
Intracystic hemorrhage with spontaneous rupture of liver cyst complicated by infection: a case report; Kanazawa A et al.; A 78-year-old man who was being followed-up for a liver cyst was admitted to Asakayama General Hospital because of the sudden onset of severe right hypochondralgia and fever, with a preceding dull pain in the right upper quadrant of the abdomen of four 'days' duration . Computed tomography revealed remarkable enlargement of the liver cyst . We diagnosed intracystic hemorrhage and spontaneous rupture of the liver cyst . As we diagnosed bacterial infection in the ruptured cyst, transhepatic cystic drainage was performed . After improving the clinical status of the patient, we injected ethanol into the cyst, inducing a significant decrease in its size . There has been a few previous reports of intracystic hemorrhage and spontaneous rupture of a liver cyst complicated by infection . Transhepatic cyst drainage combined with antibiotic therapy and intracystic ethanol injection may be a useful and minimally invasive method for liver cysts with these complications, especially in compromised patients.

Clin Pharmacol Ther, 2004 Jun, 75(6), 516 - 28
CYP3A5 genotype has a dose-dependent effect on ABT-773 plasma levels; Katz DA et al.; BACKGROUND: The metabolizing enzyme cytochrome P450 (CYP) 3A5 is polymorphically expressed as a result of genetic variants that do not encode functional protein . Because of overlapping substrate specificity with CYP3A4 and the multidrug efflux pump P-glycoprotein, the importance of CYP3A5 genetic polymorphism for pharmacokinetics is controversial . OBJECTIVE: Our objective was to determine whether genetic polymorphisms in CYP3A5 or MDR-1 (which encodes P-glycoprotein) influence the drug levels of ABT-773, a ketolide antibiotic that is a substrate for both CYP3A and P-glycoprotein . METHODS: Healthy volunteers given 3 different oral dose levels of ABT-773 were genotyped at 2 common CYP3A5 and 7 common MDR-1 polymorphisms . Individuals were categorized as CYP3A5-positive if they carried at least 1 functional CYP3A5*1 allele and as CYP3A5-negative if they did not . Area under the plasma concentration-time curves (AUCs) from 0 to 6 hours (AUC(t)) and maximum postdose plasma concentration (C(max)) after a single dose and on day 5 of a twice-daily regimen were calculated and correlated with genotypes . RESULTS: ABT-773 AUC(t) and C(max) were, on average, higher in CYP3A5-negative subjects given 450 mg ABT-773 (n = 9) than in CYP3A5-positive subjects with identical doses (n = 8) . The relationship for AUC(t) was statistically significant both after a single dose (geometric mean and 95% confidence interval {CI}, 5.0 microg.h/mL {3.9-6.4 microg.h/mL} versus 2.8 microg.h/mL {1.8-4.3 microg.h/mL}; P =.03) and on the fifth day of twice-daily dosing (12.4 microg.h/mL {8.7-17.6 microg.h/mL} versus 7.4 microg.h/mL {5.5-9.8 microg.h/mL}, P =.04) . The relationship for C(max) was statistically significant after a single dose (1220 microg/mL {867-1167 microg/mL} versus 727 microg/mL {506-1044 microg/mL}, P =.04) and showed a trend in the same direction on the fifth day of twice-daily dosing (2566 microg/mL {1813-3631 microg/mL} versus 1621 microg/mL {1122-2343 microg/mL}, P =.07) . In contrast, AUC(t) and C(max) were not significantly different between CYP3A5-positive and CYP3A5-negative individuals given 150 mg or 300 mg ABT-773 . ABT-773 plasma levels did not trend with MDR-1 genotypes . CONCLUSIONS: These results suggest that CYP3A5 genotype may be an important determinant of in vivo drug disposition and that this effect may be dose-dependent.

FEBS Lett, 2004 Jun 4, 567(2-3), 316 - 20
Insights into the specificity of RNA cleavage by the Escherichia coli MazF toxin; Munoz-Gomez AJ et al.; The mazEF (chpA) toxin-antitoxin system of Escherichia coli is involved in the cell response to nutritional and antibiotic stresses as well as in bacterial-programmed cell death . Valuable information on the MazF toxin was derived from the determination of the crystal structure of the MazE/MazF complex and from in vivo data, suggesting that MazF promoted ribosome-dependent cleavage of messenger RNA . However, it was concluded from recent in vitro analyses using a MazF-(His6) fusion protein that MazF was an endoribonuclease that cleaved messenger RNA specifically at 5'-ACA-3' sites situated in single-stranded regions . In contrast, our work reported here shows that native MazF protein cleaves RNA at the 5' side of residue A in 5'-NAC-3' sequences (where N is preferentially U or A) . MazF-dependent cleavage occurred at target sequences situated either in single- or double-stranded RNA regions . These activities were neutralized by a His6-MazE antitoxin . Although essentially consistent with previous in vivo reports on the substrate specificity of MazF, our results strongly suggest that the endoribonuclease activity of MazF may be modulated by additional factors to cleave messenger and other cellular RNAs.

Soc Sci Med, 2004 Aug, 59(4), 763 - 73
A social disease/a social response: lessons in tuberculosis from early 20th century Chile; Paluzzi JE; During the 1930s, Chile reported the world's highest mortality rate due to tuberculosis . In this pre-antibiotic era, the attention of the biomedical community frequently turned to the underlying social inequalities and deficiencies that created conditions of heightened risk for Chile's rapidly expanding working class . With the recognition that crowded housing, chronic malnutrition and substandard working conditions fostered an environment in which the disease developed and spread with virulent rapidity, physicians frequently became vocal advocates for widespread and significant social reform . However, by the time of the introduction of efficacious pharmaceutical agents in the 1940s and with the overall rapid development of biomedicine in the mid-20th century, the larger medical discourse became more rigidly defined and characterized by the promotion of the new antibiotics and treatments . These factors increased the depth of the self-defined medical territory but substantially reduced its breadth . Accompanying this shift was an increasing focus on individual behaviors that were seen as deficient and were both socially censored and used as explanations for increased susceptibility . In the midst of the current worldwide epidemic of tuberculosis, this disease and its epidemiological pattern heightens our awareness of the significance and consequences of global inequalities . It also draws our attention to the importance of intervention within the social conditions from which these patterns emerge.

Eur Respir J, 2004 May, 23(5), 714 - 7
Clarithromycin reduces the severity of bronchial hyperresponsiveness in patients with asthma; Kostadima E et al.; A randomised double-blind placebo-controlled study was designed to evaluate the effects of a semisynthetic macrolide antibiotic, clarithromycin, on bronchial hyperresponsiveness to methacholine in patients with a diagnosis of asthma . Adult asthma patients undergoing treatment with budesonide 400 microg b.i.d . and salbutamol 200 microg p.r.n . less than twice weekly were studied . Arm A (16 males/six females, aged 48 +/- 16 yrs) received clarithromycin 250 mg b.i.d . for 8 weeks, arm B (eight males/12 females, aged 42 +/- 12 yrs) clarithromycin 250 mg t.id . and arm C (six males/15 females, aged 41 +/- 16 yrs) placebo dextrose tablets . Bronchial hyperresponsiveness was quantified by measurement of the provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (PD20) . Median (interquartile range) PD20 in the three groups before and after treatment with clarithromycin were: arm A: 0.3 (0.1-1) and 1.3 (0.6-2) mg; arm B: 0.4 (0.1-0.9) and 2 (2-2) mg; and arm C: 0.4 (0.1-0.9) and 0.3 (0.1-0.6) mg, respectively . Serum free cortisol levels were determined and remained unchanged from baseline in the clarithromycin-treated patients . It is concluded that clarithromycin reduces the degree of bronchial hyperresponsiveness in patients with asthma.

Eur Respir J, 2004 May, 23(5), 692 - 7
Inhaled corticosteroids and the risk of a first exacerbation in COPD patients; de Melo MN et al.; The role of inhaled corticosteroids (ICS) in asthma is well established, but their benefit in the management of chronic obstructive pulmonary disease (COPD) is still controversial . The current study assessed whether ICS are effective in preventing a first exacerbation of COPD . A cohort of newly treated COPD patients was formed from the Administrative Databases of Saskatchewan Health . The outcome was the occurrence of a first moderate or severe exacerbation from 1990-1999 . Moderate exacerbations involved prescriptions for an antibiotic and an oral corticosteroid on the same day . Severe exacerbations were hospitalisations with a primary discharge diagnosis of COPD . A nested case-control design was used and matched on year of birth and cohort entry . Rate ratios (RR) were further adjusted for use of other medication and other confounders . There were 995 exacerbations among 4,455 subjects . The rate of a first exacerbation was increased with any use of ICS in the year prior to the index date (RR: 1.27; 95% CI: 1.08-1.48) and with current use (RR: 1.51; 95% CI: 1.22-1.87), and it increased with increasing daily doses of ICS . Inhaled corticosteroids do not seem to be beneficial in reducing the risk of a first exacerbation of chronic obstructive pulmonary disease.

Allergy Asthma Proc, 2004 Mar-Apr, 25(2), 95 - 6
New thoughts on sinus headache; Tepper SJ; Sinus headache is not a recognized entity by allergy, otolaryngology, or neurological organizations . Headache is a minor feature in the diagnosis of acute rhinosinusitis and is not validated as a symptom in chronic sinusitis . Sinus headaches are self-diagnosed due to weather triggers, bilateral and frontomaxillary location, and the presence of vasomotor signs and symptoms, all of which can accompany the migraine . Over 90% of self-diagnosed and doctor-diagnosed sinus headaches meet the International Headache Society criteria for migraines, and those migraines misdiagnosed as sinus headaches respond to sumatriptan better than placebo because migraines respond to triptans . Sinus headaches are usually severely disabling migraines, misdiagnosed and mistreated, with 61% of patients receiving antibiotic prescriptions for noninfectious causes, thus failing the patients and, in addition, contributing to a serious public health problem.

Pol Merkuriusz Lek, 2004 Feb, 16(92), 191 - 3
{Role of the State Sanitary Inspection in supervision over nosocomial infections}; Grabowski ML; Suitably conducted monitoring of nosocomial infections in Polish health care centers would be a proof of the quality of medical services for the Polish society . However, because of some organizational and financial negligence from previous years, the Ministry of Health services are implementing practical and scientific rules of the nosocomial infections monitoring, through the implementation of systemic solutions, recommendations and suitable procedures . The State Sanitary Inspection has prepared a modern amendment of the act of communicable diseases and infections, which will help with proper enforcement of reliable reports and registers conducted by professional groups and existing committees for nosocomial infection control . We can expect that suitably conducted, hospital antibiotic policy, the use of medical science in the above-mentioned scope, reliable comparing analyses, as well as drug resistance monitoring will bring clearly defined effects, such as: reduction of expenditures on health care, as well as lessening of hospitalization duration.

Am J Infect Control, 2004 Jun, 32(4), 209 - 14
Nosocomial pneumonia in the intensive care unit of a Brazilian university hospital: an analysis of the time span from admission to disease onset; Gusmao ME et al.; BACKGROUND: In addition to controversies as to the definition of nosocomial pneumonia (NP) because of the lack of a widely accepted diagnostic standard, there has been no agreement concerning the time span from hospital admission to disease onset . This study aims at both estimating the time span, in hours, from admission to the occurrence of suspected NP and investigating risk factors that might influence this time span . METHODS: This is a cohort study, and subjects were patients with nosocomial infection acquired in the intensive care unit of Edgard Santos University Hospital (HUPES/ICU) in Salvador, Brazil, from January 1995 to December 1997 . Patients were observed from admission to 48 hours after discharge from the intensive care unit . The time span from admission to occurrence of suspected NP, the reason for admission, patient's origin, history of surgery, general anesthesia, mechanical ventilation, and use of antibiotic were analyzed and given a multivariate analysis using Cox regression model . RESULTS: Among 246 patients with nosocomial infection, 198 (80.5%) were suspected cases of NP, whereas 48 patients (19.5%) were not classified as such . The mean time, in hours, for the NP-free time span was 85.1 +/- 3.5 hours, and the median time was 72 hours when estimated by Kaplan-Meier method . Patients admitted from surgical heart procedures who had been given general anesthesia, mechanical ventilation, and antibiotics showed statistically significant shorter mean time spans from admission to NP occurrence when compared with the other patients . Age >or=50 years, use of mechanical ventilation, and use of antibiotics were associated with NP . CONCLUSIONS: Our finding for the estimated mean NP-free time span at the HUPES/ICU is somewhat in accordance with the literature (48 to 72 hours) . Patients at HUPES/ICU might be considered as showing early NP, because they were diagnosed before the 5th day after admission . Preventive measures to NP should be reviewed and intensified at the HUPES/ICU, especially as related to mechanical ventilation.

Proc Natl Acad Sci U S A, 2004 Aug 17, 101(33), 11977 - 9 Epub 2004 Jun 02.
Total synthesis and structure of the ramoplanin A1 and A3 aglycons: two minor components of the ramoplanin complex; Shin D et al.; Ramoplanin is a potent antibiotic, first disclosed in 1984, that acts by inhibiting bacterial cell-wall biosynthesis . The original ramoplanin complex was shown to consist of a mixture of three closely related compounds, ramoplanin A1-A3, of which ramoplanin A2 is the most abundant . The structure of ramoplanin A2 was unambiguously established first through a series of extensive spectroscopic studies, allowing complete stereochemical assignments and subsequently providing a minor reassignment of the side-chain double-bond stereochemistry and, most recently, through total synthesis of authentic material . Here we report the total syntheses of the aglycons of the minor components of the ramoplanin complex, A1 and A3, which unambiguously establish their structure and provide an expected structural revision for the lipid side-chain double-bond stereochemistry.

Expert Opin Investig Drugs, 2004 Jun, 13(6), 673 - 9
Immunotherapeutics for nosocomial infections; Patti JM; Nosocomial or hospital-acquired infections are associated with prolonged hospitalisation and increased healthcare costs and resource utilisation . Continued advances in sophisticated medical procedures, an increase in the number of immunocompromised patients and a steady rise in the prevalence of antibiotic-resistant organisms has renewed interest in the development of novel therapies that can treat nosocomial infections . This review focuses on novel immunological approaches to address this significant unmet medical need.

Fiziol Zh, 2004, 50(2), 49 - 63
{Aging-related increase of sensitivity of the mitochondrial permeability transition pore to inductors in the rat heart}; Sahach VF et al.; An age-related increase in the sensitivity of the mitochondrial permeability transition pore (MPTP) to inductors of it's opening, Ca2+ ions and phenylarsineoxide (PAO) was studied in experiments in vitro on isolated heart mitochondria of adult and old rats . Two indices were measured spectrophotometrically (lambda = 520 nm) by a decrease in an optical density (OD), resulting from mitochondrial swelling and a release of mitochondrial unidentified substances (mitochondrial factor, MF) registered also spectrophotometrically in a range of waves lambda = 230-260 nm . Dose-dependent effect of Ca2+ (10(-7)-10(-4) mol/l) and PAO (10(-8)-10(-4) mol/l) on swelling of the mitochondria were observed in samples from both adult and old rats . Swelling of the mitochondria from the heart of old rats induced by application of the above inductors was more intensive than the respective effect in samples from adult rats . In samples from the heart of both adult and old rats Ca2+ ions within the tested concentration range (10(-7)-10(-4) mol/l) evoked the release of MF in a dose-dependent manner . Mitochondria from the heart of old rats were found to be capable of releasing some amounts of MF in the absence of the MPTP inductors PAO . When this inductor was applied in a 10(-9) to 10(-4) mol/l concentration range, isolated mitochondria from the heart of old rats released unidentified substances with the absorption peaks at two wavelength, lambda = 230 nm and lambda = 240-245 nm . The former peak was found to be Cyclosporin A-insensitive, while the latter peak could be practically completely inhibited by this antibiotic . The concentrations of tested solutions (10(-7) mol/l CaCl2 and 10(-9) mol/l PAO), at which the release of the factor from the mitochondria of the old rat heart was observed, were significantly lower than those in adult rats . Our experimental data show that mitochondria isolated from the heart tissue of old rats demonstrate significantly higher sensitivity to inductors of MPTP-opening, Ca(2+)-overload and PAO as compared to that typical of adult animals . A higher sensitivity of MPTP-opening in the heart of old rats was accompanied by a higher basal level of expression of mRNA of the bax gene, as compared to that found in adult animals . The expression of the bcl-2 gene showed no age group-related differences . It can be supposed that a proapoptotic agent, the Bax protein, is related to an increase in the sensitivity of the MPTP (in particular to that manifested in the processes of pore formation) in the course of aging . Antioxidants, melathonin and trolox, when applied in 10(-5) mol/l concentration, presented to a certain extent opening of the MPTP-induced by 10(-5) mol/l PAO in samples from adult and old rats . These findings can be used for correction of increased sensitivity of the MPTP to different inductors, which is typical of old rats . We conclude that physiological aging is accompanied by the mitochondrial dysfunction . The MF-released capability of the mitochondria from heart tissue of old rats observed both in the presence and absence of MPTP-opening inductors (probably related to a higher sensitivity of MPTP-opening) is one of the manifestation of such dysfunction.

Cancer Chemother Pharmacol, 2004 Sep, 54(3), 249 - 58 Epub 2004 Jun 02.
Mechanistic and antineoplastic evaluation of taurolidine in the DU145 model of human prostate cancer; Darnowski JW et al.; Taurolidine (TRD) was designed in the 1970s as a broad-spectrum antibiotic and is used clinically at high doses without systemic toxicity . We have found that this agent possesses cytotoxic activity in human tumor cell lines and antineoplastic activity in mice bearing i.p . human tumor xenografts . We now report the mechanism by which TRD induces cell death in DU145 human prostate tumor cells . The IC50 (3 days) of TRD in this model was 16.8+/-1.1 microM . Cytotoxicity was associated with DNA debris and increased membrane phosphatidylserine externalization, both suggesting the induction of apoptosis . This was confirmed by the ability of TRD to induce PARP cleavage in these cells, an effect prevented by coexposure to the pan-caspase inhibitor zVAD-FMK . TRD exposure also resulted in the appearance of cytochrome c in the cytoplasm, procaspase 9 activation within 2 h of drug exposure and procaspase 8 activation 4 h after exposure . Parallel experiments revealed that cytochrome c appearance in the cytoplasm was not blocked by preexposure to zVAD-FMK, while activation of both procaspase 9 and procaspase 8 was prevented . Finally, antineoplastic activity was assessed in mice bearing subcutaneous xenografts of DU145 cells . Initial studies quantitated the toxicity of three i.p . injections of TRD, administered as one injection on three alternate days per week, at doses ranging from 500 to 700 mg/kg per injection . The 500 mg/kg dose produced about 7% mortality after three cycles and effectively inhibited tumor growth . Thus, TRD induced mitochondrial-mediated apoptosis in DU145 human prostate tumor cells and this effect could be exploited for therapeutic advantage.

Neurobiol Aging, 2004 May-Jun, 25(5), 629 - 37
Challenges and directions for the pathogen hypothesis of Alzheimer's disease; Robinson SR et al.; This paper critically reviews the possibility that infiltration of the brain by pathogens (e.g . Herpes simplex virus type 1 (HSV1) or Chlamydophila pneumoniae (Cp)) acts as a trigger or co-factor for Alzheimer's disease (AD) . The evidence currently available is limited and in some cases inconsistent, but it does justify the need for more vigorous investigation of this hypothesis . An issue of particular concern is the paucity of experimental evidence showing that pathogens can elicit the neuropathological changes and cognitive deficits that characterise AD . Other weaknesses include a failure to obtain independent confirmation of Cp in AD brains, and a lack of evidence for HSV1 proteins or intact virions in AD brain tissue . Future avenues of investigation that might prove fruitful include epidemiological investigations of the incidence of AD in individuals who are either immunosuppressed or have received chronic antiviral or antibiotic therapy . There is also a need to consider systemic infections as potential contributors to the pathogenesis of AD.

Ann Transplant, 2003, 8(4), 46 - 9
Application of biological dressings from radiosterilized amnios with cobalt 60 and serologic studies on the handling of burns in pediatric patients; Ley-Chavez E et al.; We present the use of biological dressing (amnios) as an alternative for skin replacement due to burn accidents . With the use of serologic tests, it is guaranteed to be free of the possibility of transmitting infectious diseases . The amnios is sterilized with 60Co gamma radiation . In this way, amnios is free of bacteria and fungi . In addition, with the use of serologic tests at the moment of the childbirth and 6 months later, we can be sure that it won't transmit the syphilis, AIDS, hepatitis b and c viruses . This treatment was applied to 12 children with burns of 1 degree and 2 degrees degree (7 girls and 5 boys) that required hospitalization . The application is very simple . It does not require of anesthesic procedure, or the use of surgical room . The pain decreased notoriously, and the procedure can be repeated as frequently as necessary . Once the dressing is applied, it does not require any type of surgical cleaning . The scaring process begins at the borders and under the dressing, where there is a new tissue . It decreases: 1) the possibility of infection, and therefore reduces the consumption of antibiotic; 2) the use of analgesics; 3) the time of scaring and 4) the number of days of hospitalization.

J Indian Med Assoc . 2003 Sep;101(9):532, 534, 536.
Leptospirosis and Weil's disease in eastern India; Basu D et al.; Leptospirosis is characterised by a broad spectrum of clinical manifestations varying from inapparent infection to fulminant fatal disease . Severe leptospirosis characterised by profound jaundice is referred to as Weil's disease . In the present study 20 patients of leptospirosis, of which 7 belonged to Weil's disease, were diagnosed based on the demonstration of IgM antileptospira antibody and supported by clinical correlation and appropriate biochemical markers . Overall, the male and female ratio was 17:3 and the same ratio for the Weil's disease was 6:1 . The most common presentation involved fever, malaise and myalgia . Conjunctival congestion was found in 75% of the cases and jaundice was encountered in 90% of the cases . The prognosis of all these patients, including that of Weil's disease was excellent . Early recognition and initiation of antibiotic therapy were found to be important.

J Bioenerg Biomembr, 2004 Feb, 36(1), 143 - 50
Novel functional aspects of the membrane-bound exo-pyrophosphatase of the hyperthermoacidophilic archaeon Sulfolobus are provided by analysis of its gene and the adjacent gene cluster; Moll RG et al.; The gene of the previously described plasma-membrane-bound acidic pyrophosphatase (exo-PPase) and adjacent genes of the hyperthermoacidophilic crenarchaeon Sulfolobus acidocaldarius (DSM 639) were cloned and sequenced . The 4-kb gene cluster comprises four open reading frames (sepp, simp, sabc, and satr) encoding the pyrophosphatase, a small hydrophobic protein of unknown cellular function, a hydrophilic ABC transport ATPase, and an amino transferase . The four proteins have deduced molecular masses of 21, 16, 34, and 48 kDa, respectively . Sepp, simp, and sabc are transcribed as monocistronic mRNAs from which sepp and sabc have been heterologously expressed by in vitro translation using reticulocyte lysates . The Sulfolobus acidocaldarius acidic exo-pyrophosphatase is a membrane-residing protein anchored with five transmembrane alpha-helices . Alignments with protein sequences from databases together with predictions of membrane topology reveal a novel group of proteins with the conserved phosphatase motif KxxxxxRP-(x12-54)-PSGH-(x31-54)-SRxxxxxHxxxD . For none of them a phosphatase or pyrophosphatase activity has yet been described except for the authentic Sulfolobus acidocaldarius protein . On the basis of these investigations a direct role of the exo-PPase in dolichyl phosphate or pyrophosphate hydrolysis and in resistance to the peptide antibiotic bacitracin is discussed.

Appl Microbiol Biotechnol, 2004 Oct, 65(5), 593 - 9 Epub 2004 May 27.
Cloning of glyceraldehyde-3-phosphate dehydrogenase gene and use of the gpd promoter for transformation in Flammulina velutipes; Kuo CY et al.; The glyceraldehyde-3-phosphate dehydrogenase gene of Flammulina velutipes was isolated . The complete gpd sequence (from ATG to TAA) was 1,489 bp in length and contained nine introns . The locations of these nine introns were similar to those of other basidiomycetes, which might reflect the evolutionary divergence of these mushrooms . The F . velutipes gpd gene was found to encode a protein of 339 amino acids and its putative amino acid sequence revealed a high similarity to an analogous protein deriving from other basidiomycetes . Results of Southern blot analysis suggested that there existed only one copy of the gpd gene in the genome of F . velutipes and that there was one typical TATA box and two CAAT boxes located in the 5' flanking region . The F . velutipes gpd promoter was fused to a hygromycin B phosphotransferase gene (hph) derived from Escherichia coli as a selection marker . Using the resulting construction, hph was efficiently transformed into F . velutipes by basidiospore electroporation . No false-positive antibiotic-resistant cultures were detected by PCR amplification and the hygromycin resistance trait was maintained stably during mitotic cell division for 3 months . Southern analysis of transformants indicated the integration of gene might occur by non-homologous recombination . This rapid and convenient electroporation procedure offers new prospects for the genetic manipulation and a tool for tagging genes of this important edible mushroom species . Sequence data will appear in the DDBJ/EMBL/GenBank nucleotide sequence database under accession number AF515622.

Eur J Emerg Med, 2004 Feb, 11(1), 49 - 51
Necrotizing fasciitis of the leg presenting with chest wall emphysema; Geusens E et al.; We present the case of a 70-year-old woman with necrotizing fasciitis of the right leg, sepsis and bacteraemia with Escherichia coli . Chest wall emphysema, detected on standard radiograph and the presence of air in the soft-tissue of the foot was the reason for prompt surgical drainage in addition to standard fluid resuscitation and antibiotic therapy . There was no evidence of underlying diabetes mellitus, but unknown chronic renal failure and corticosteroid therapy for rheumatoid arthritis were considered predisposing factors . We present a short overview of this rare life-threatening condition with emphasis on radiological diagnostic modalities.

Eur J Gastroenterol Hepatol, 2004 Jun, 16(6), 579 - 83
Diagnosis of spontaneous bacterial peritonitis in cirrhotic patients by use of two reagent strips; Thevenot T et al.; OBJECTIVE: Spontaneous bacterial peritonitis (SBP) is one of the potentially life-threatening complications in ascitic cirrhotic patients with a mortality rate ranging between 30 and 50% . The improved survival might be explained by a more rapid diagnosis and treatment . The aim of our study was to assess the utility of two reagent strips, the Multistix test and the Combur(2) test LN, for the rapid diagnosis of SBP . METHODS: Thirty-one unselected consecutive cirrhotic patients with ascites were included and a total of 100 paracenteses were performed . All ascitic fluid was analysed with the two reagent strips, leucocyte and polymorphonuclear (PMN) leucocyte cell count and blood-bottle culture if the strips were positive . The strips were considered positive if the colour turned to purple: i.e . grade 3 or 4 for the Multistix test and 2 or 3 for the Combur(2) test LN on a colorimetric scale . RESULTS: We diagnosed nine infections of which four were SBP defined by PMN > or = 250 cells/mm(3) and a positive culture in ascitic fluid and five were culture negative neutrocytic ascites (PMN > or = 250 cells/mm(3) and a negative culture) . The results of the two strips were concordant and were negative in only one SBP . The sensitivity, specificity, positive and negative predictive values of these two strips were 89%, 100%, 100% and 99%, respectively . CONCLUSIONS: These reagent strips are very sensitive and specific for the diagnosis of SBP, allowing immediate commencement of empirical antibiotic therapy . These strips should be used for the diagnosis of SBP, especially on an emergency basis.

Ann Surg, 2004 Jun, 239(6), 752 - 60; discussion 760-2
Practicing surgeons lead in quality care, safety, and cost control; Shively EH et al.; OBJECTIVE: To report the experiences of 66 surgical specialists from 15 different hospitals who performed 43 CPT-based procedures more than 16,000 times . SUMMARY BACKGROUND DATA: Surgeons are under increasing pressure to demonstrate patient safety data as quantitated by objective and subjective outcomes that meet or exceed the standards of benchmark institutions or databases . METHODS: Data from 66 surgical specialists on 43 CPT-based procedures were accessioned over a 4-year period . The hospitals vary from a small 30-bed hospital to large teaching hospitals . All reported deaths and complications were verified from hospital and office records and compared with benchmarks . RESULTS: Over a 4-year inclusive period (1999-2002), 16,028 elective operations were accessioned . There was a total 1.4% complication rate and 0.05% death rate . A system has been developed for tracking outcomes . A wide range of improvements have been identified . These include the following: 1) improved classification of indications for systemic prophylactic antibiotic use and reduction in the variety of drugs used, 2) shortened length of stay for standard procedures in different surgical specialties, 3) adherence to strict indicators for selected operative procedures, 4) less use of costly diagnostic procedures, 5) decreased use of expensive home health services, 6) decreased use of very expensive drugs, 7) identification of the unnecessary expense of disposable laparoscopic devices, 8) development of a method to compare a one-surgeon hospital with his peers, and 9) development of unique protocols for interaction of anesthesia and surgery . The system also provides a very good basis for confirmation of patient safety and improvement therein . CONCLUSIONS: Since 1998, Quality Surgical Solutions, PLLC, has developed simple physician-authored protocols for delivering high-quality and cost-effective surgery that measure up to benchmark institutions . We have discovered wide areas for improvements in surgery by adherence to simple protocols, minimizing death and complications and clarifying cost issues.

Surg Neurol, 2004 Jun, 61(6), 515 - 22; discussion 522
Adopting 540-degree fusion to correct cervical kyphosis; Sin AH et al.; BACKGROUND: Two cases of severe cervical spine kyphotic deformity resulting from late effects of infection were successfully corrected by combined anterior and posterior instrumentations in a single operative sitting . CASE DESCRIPTION: Case 1 is a 43-year-old man who developed severe cervical kyphosis from C5-6 discitis over a few months despite long-term antibiotic therapy . He was neurologically intact except for severe neck pain and obvious deformity . Case 2 is a 40-year-old woman who had a previous wound infection five years before presentation . There was gradual worsening of swan neck deformity at the C2-3 and C5-6 levels with some spinal cord compression worsening her baseline myelopathy . The patients were placed and maintained in cervical traction on the Stryker frame for the duration of the procedure . Both cases required anterior approach initially to achieve some release of dense scar tissue using a high-speed drill . The wounds were then closed and patients were rotated to the prone position for further release of fused bony elements, including the facets . Lateral mass screws and plates were placed . In Case 2, additional instrument to the occipital was performed to stabilize the C2 using a U-shaped cervical rod . Once adequate reduction had been achieved, the patients were rotated back to supine position for further corpectomy and fibular construct fusion with plates . CONCLUSION: In cases of severe kyphotic deformity complicating infectious vertebral destruction, the spinal alignment can be achieved safely by a multi-step technique combining the anterior as well as posterior surgical approaches.

Acta Orthop Belg, 2004 Apr, 70(2), 162 - 5
The spacer block technique in osteomyelitis of the phalangeal bones of the hand; Proubasta IR et al.; The authors report a case of an open mallet injury with a traumatic arthrotomy which was complicated with a destructive infection involving both the middle and distal phalanges of a ring digit and which was treated with two-stage reconstructive surgery with good results . In the first stage, after the osteomyelitic portion of adjacent phalangeal bones were excised en bloc, the dead space was filled by means of an antibiotic-impregnated cement spacer . In the second stage, an autogenous corticocancellous bone graft from the iliac crest was secured into the defect with a intramedullary Herbert scaphoid screw.

Clin EEG Neurosci, 2004 Apr, 35(2), 100 - 3
Encephalopathy secondary to imipenem therapy; Fernandez-Torre JL et al.; We describe the case of an 84-year-old woman who developed a confusional state and suffered from a generalized tonic-clonic seizure while she was treated with imipenem, a beta-lactam antibiotic . Focal and generalized epileptiform discharges and a photoparoxysmal response were prominent with transient changes on the EEG.

Ann Vasc Surg, 2004 Jul, 18(4), 481 - 3
Acute appendicitis-like symptoms as initial presentation of ovarian vein thrombosis; Prieto-Nieto MI et al.; Postpartum ovarian vein thrombosis is a rare condition, with an incidence rate being 1/600 deliveries . It most often arises in the right ovarian vein . A 33-year-old patient who had had normal vaginal delivery presented with fever, pain in the right iliac fossa, and leukocytosis on the sixth day after delivery . An antibiotic course was instituted but 3 days later symptoms reappeared . Diagnosis of acute appendicitis was made . At surgery through a McBurney incision, a woody tumoration consistent with ovarian vein thrombosis was found . Anticoagulation therapy with heparin and antibiotics were instituted . Phlebography and color Doppler sonography confirmed the presence of thrombosis of both the common femoral iliac and inferior vena cava . Fribrolysis with urokinase was performed . The patient has remained stable and symptom-free over a 4-year follow-up . Ovarian vein thrombosis typically presents with symptoms suggestive of acute appendicitis, as was the case in our patient . Color Doppler sonography is the favored diagnostic procedure, with CT being a supplementary tool . Surgery is not necessary and treatment consists of anticoagulants and antibiotics . Even though postpartum ovarian vein thrombosis is rare, early recognition of the condition is of paramount importance to institute the adequate treatment and avoid potential serious sequelae.

Knee Surg Sports Traumatol Arthrosc . 2004 May 25; {Epub ahead of print}
Knee arthrodesis using circular external fixator in the treatment of infected knee prosthesis: case report; Gunes T et al.; A patient (68 years old and male) underwent total knee replacement because of arthrosis, but he subsequently had infection due to a wound problem . Although he underwent early debridement, antibiotherapy, and soft-tissue operation, treatment failed because of improper soft-tissue coverage and progression of the infection . Therefore, the prosthesis was removed and a spacer with antibiotic was placed, in order to provide soft-tissue coverage and to eradicate infection . After 2 months, the patient underwent knee arthrodesis using a circular external fixator to achieve a stable lower extremity and to facilitate return to activities of daily living . We obtained knee fusion at 4 months without any requirement for secondary procedure of soft tissue and bone graft . There was no major complication . Arthrodesis with circular external fixator is a reliable and successive method that should be preferred for the treatment of infected knee replacement.

Nature . 2004 May 27;429(6990):363.
Pigment chemistry: the red sweat of the hippopotamus; Saikawa Y et al.; Within a few minutes of perspiration, the colourless, viscous sweat of the hippopotamus gradually turns red, and then brown as the pigment polymerizes . Here we isolate and characterize the pigments responsible for this colour reaction . The unstable red and orange pigments turn out to be non-benzenoid aromatic compounds that are unexpectedly acidic and have antibiotic as well as sunscreen activity.

Virus Res, 2004 Jul, 103(1-2), 177 - 85
Current status of live attenuated influenza virus vaccine in the US; Belshe RB; The efficacy and effectiveness of cold adapted live attenuated (CAIV-T, FluMist intranasal influenza vaccine is reviewed . CAIV-T consists of approximately 10(7) TCID50 per dose of each influenza A/H1N1, influenza A/H3N2, and influenza B vaccine strain . The exact strains are updated each year to antigenically match the antigens recommended by national health authorities for inclusion in the vaccine . In one year in which the vaccine strain did not well match the epidemic strain, the live attenuated vaccine induced a broad immune response that cross-reacted significantly with the drifted strain . The efficacy of CAIV-T in adults was demonstrated with challenge studies and the effectiveness of the vaccine for reducing febrile upper respiratory illness, days of missed work, and days of antibiotic use was demonstrated in a large field trial . In young children, protective efficacy against culture confirmed influenza was demonstrated in a field trial with overall protective efficacy of 92% during a two year study . Vaccine was also highly protective against a strain not contained in the vaccine, with 86% protective efficacy demonstrated against this significantly drifted virus . Effectiveness measures, including protection against febrile otitis media and visits to the doctor were demonstrated . Live attenuated vaccine provides a significant new tool to help prevent influenza.

J Med Chem, 2004 Jun 3, 47(12), 3308 - 19
Mitomycin dimers: polyfunctional cross-linkers of DNA; Paz MM et al.; The three dimers 3, 4, and 5 of mitomycin C (MC), a natural antibiotic and cancer chemotherapeutic agent, were synthesized in which two MC molecules were linked with -(CH(2))(4)-, -(CH(2))(12)-, and -(CH(2))(3)N(CH(3))(CH(2))(3)- tethers, respectively . The dimeric mitomycins were designed to react as polyfunctional DNA alkylators, generating novel types of DNA damage . To test this design, their in vitro DNA alkylating and interstrand cross-linking (ICL) activities were studied in direct comparison with MC, which is itself an ICL agent . Evidence is presented that 3-5 multifunctionally alkylate and cross-link extracellular DNA and form DNA ICLs more efficiently than MC . Reductive activation, required for these activities, is catalyzed by the same reductases and chemical reductants that activate MC . Dimer 5, but not MC, cross-linked DNA under activation by low pH also . Sequence specificities of cross-linking of a 162-bp DNA fragment (tyrT DNA) by MC, 3, and 5 were determined using DPAGE . The dimers and MC cross-linked DNA with the same apparent CpG sequence specificity, but 5 exhibited much greater cross-linking efficacy than MC . Greatly enhanced regioselectivity of cross-linking to G.C rich regions by 5 relative to MC was observed, for which a mechanism unique to dimeric MCs is proposed . Covalent dG adducts of 5 with DNA were isolated and characterized by their UV and mass spectra . Tri- and tetrafunctional DNA adducts of 5 were detected . Although the dimers were generally less cytotoxic than MC, dimer 5 was highly and uniformly cytotoxic to all 60 human tumor cell cultures of the NCI screen . Its cytotoxicity to EMT6 tumor cells was enhanced under hypoxic conditions . These findings together verify the expected features of the MC dimers and warrant further study of the biological effects of dimer 5.

J Am Geriatr Soc, 2004 Jun, 52(6), 875 - 9
Office evaluation and treatment of elderly patients with acute bronchitis; Steinman MA et al.; OBJECTIVES: To assess the office evaluation of seniors with uncomplicated acute bronchitis and to determine the association between elements of the clinical evaluation and antibiotic prescribing decisions . DESIGN: Cross-sectional chart review . SETTING: Seventy-seven community-based office practices in the Denver metropolitan area . PARTICIPANTS: Elderly fee-for-service Medicare patients . MEASUREMENTS: Medicare administrative data to identify patients with acute bronchitis; medical record review to confirm the diagnosis and record other clinical data . Results: Of 198 elderly patients with acute bronchitis, the mean age+/-standard deviation was 76+/-8.6; 53% had at least one comorbid condition . Clinically important vital signs were frequently not recorded; temperature was missing from 34% of charts and pulse from 50% of charts . When recorded, significant vital sign abnormalities were uncommon, with 7% having a temperature of 100 degrees F and 8% having a pulse of 100 beats per minute or greater . However, antibiotics were prescribed to 83% of patients, with more than half of these prescriptions being for extended-spectrum antibiotics . Treatment with antibiotics was more common in men than women (92% vs 78%, P=.007) but was not associated with clinical factors including vital sign measurement, vital sign results, chest radiography, patient age, duration of illness, or the presence of comorbidities . CONCLUSION: The vast majority of seniors with acute bronchitis are treated with antibiotics, regardless of patient characteristics or the type of evaluation received . Reducing inappropriate antibiotic use in seniors with acute bronchitis may depend on improving the evaluation of these patients and encouraging clinicians to act appropriately on the results.

Vestn Otorinolaringol, 2004, (3), 20 - 3
{Modern characteristics of clinical course and treatment of otogenic purulent meningitis}; Gadzhimirzaev GA et al.; A total of 170 patients aged 2.5 to 60 years have received treatment for otogenic meningitis caused by acute (n=37, 21.2%) or chronic otitis media (n=137, 78.2%) . Otogenic meningitis ran atypically with masked clinical manifestations in 32.2% patients . It is thought justified to repeat an antibiotic injection into the cerebrospinal canal in a severe course of meningitis, especially in combination of meningitis with other forms of intracranial complications . If clinical signs of acute otitis media and meningitis manifested weakly and, therefore, otogenic nature of meningitis is questionable, it is recommended to implement an expectant treatment policy . The absence of noticeable positive shifts in the course of the disease after several days of intensive conservative treatment is an indication for surgical intervention.

Ann Emerg Med, 2004 Jun, 43(6), 770 - 82
The emergency department community-acquired pneumonia trial: Methodology of a quality improvement intervention; Yealy DM et al.; Community-acquired pneumonia causes more than 4 million episodes of illness each year and has high morbidity, mortality, and total cost of care . Nationwide, nearly 75% of community-acquired pneumonia patients are initially evaluated and treated in hospital-based emergency departments (EDs) . Substantial variation exists in illness severity assessment, hospital admission decisions, and performance of recommended processes of care . We designed an ED-based quality improvement trial focused on the initial care of patients with community-acquired pneumonia . We used the Pneumonia Severity Index and level of arterial oxygenation to identify patients at low risk for 30-day mortality and to guide admission decisionmaking . We assessed the performance of recommended "best practices," consisting of assessment of arterial oxygenation, the collection of blood cultures for inpatients, and the timely initiation of appropriate empiric antibiotic therapy for inpatients and outpatients . We conducted a 32-site, cluster-randomized trial in Pennsylvania and Connecticut, comparing the effectiveness and safety of 3 guideline implementation strategies of increasing intensity . The multifaceted implementation plans were carried out in conjunction with each state's quality improvement organization . This article describes the background, objectives, and methodology of this trial to translate evidence-based knowledge on the quality and efficiency of care for community-acquired pneumonia into clinical practice.

Acta Crystallogr D Biol Crystallogr, 2004 Jun, 60(Pt 6), 1118 - 20 Epub 2004 May 21.
Crystallization and preliminary crystallographic data of SnoaL, a polyketide cyclase in nogalamycin biosynthesis; Sultana A et al.; Nogalonic acid methyl ester cyclase (SnoaL) catalyzes the last ring-closure step in the biosynthesis of the polyketide antibiotic nogalamycin . Crystals of a complex of SnoaL with the substrate nogalonic acid methyl ester have been obtained using PEG 4000 as precipitant . The crystals are orthorhombic, space group I222, with unit-cell parameters a = 69.1, b = 72.0, c = 65.4 angstroms . They diffract to 1.35 angstroms resolution using synchrotron radiation . A Matthews coefficient of 2.0 angstroms3 Da(-1) suggests one subunit in the asymmetric unit . Diffraction data for an isomorphous uranium derivative were collected and a difference Patterson map showed strong peaks which allowed determination of the position of the uranium ions .

Drug Resist Updat, 2004 Apr, 7(2), 111 - 23
Evolution of the serine beta-lactamases: past, present and future; Hall BG et al.; We present a protein structure-based phylogeny of Classes A, C and D of the serine beta-lactamases, and a new, detailed, sequence-based phylogeny of the Class A beta-lactamases . In addition, we discuss the historical evolution of Classes C and D . The evolutionary histories of all three classes indicate that the serine beta-lactamases are ancient enzymes, originating over two billion years ago, and that some have been on plasmids for millions of years . We also discuss the recent, antibiotic-era, evolution of the serine beta-lactamases in response to the clinical use of beta-lactam antibiotics . We also discuss a method that is being used to predict the future evolution of beta-lactamases in response to selection with new drugs.

Arch Biochem Biophys, 2004 Jun 15, 426(2), 250 - 7
Cloning and expression of the trehalose-phosphate phosphatase of Mycobacterium tuberculosis: comparison to the enzyme from Mycobacterium smegmatis; Edavana VK et al.; Two open reading frames in the Mycobacterium tuberculosis genome, Rv3372 and Rv2006, have about 25% sequence identity at the amino acid level to the trehalose-phosphate phosphatase (TPP) purified from Mycobacterium smegmatis . However, the protein produced from the cloned Rv3372 gene has a molecular weight of about 45kDa whereas the trehalose-P phosphatase purified from M . smegmatis has a molecular weight of about 27kDa . We expressed the Rv3372 protein in Escherichia coli and show here that it is a trehalose-P phosphatase with very similar properties to the M . smegmatis TPP, i.e., complete specificity for trehalose-phosphate as the substrate, an almost absolute requirement for Mg(2+), and a pH optimum of 7-7.5 . On the other hand, in contrast to the M . smegmatis enzyme, the Rv3372 protein was much less stable to heat and much less sensitive to inhibition by diumycin and moenomycin . In fact, both of these antibiotics stimulate enzyme activity at low concentrations and only inhibit the activity at higher antibiotic concentrations . Antibody prepared against the 27kDa TPP does not cross react with the 45kDa TPP nor does antibody against the 45kDa TPP cross react with the 27kDa TPP . Nevertheless, studies of secondary structure by circular dichroism indicate that the two enzymes are quite similar in structure . The product of the other gene, Rv2006, is a 159kDa protein with no detectable phosphatase activity . Thus, its function is currently unknown.

Chem Biol, 2004 May, 11(5), 703 - 11
Identification of selective inhibitors for the glycosyltransferase MurG via high-throughput screening; Hu Y et al.; Nucleotide-glycosyltransferases (NDP-Gtfs) play key roles in a wide range of biological processes . It is difficult to probe the roles of individual glycosyltransferases or their products because, with few exceptions, selective glycosyltransferase inhibitors do not exist . Here, we investigate a high-throughput approach to identify glycosyltransferase inhibitors based on a fluorescent donor displacement assay . We have applied the screen to E . coli MurG, an enzyme that is both a potential antibiotic target and a paradigm for a large family of glycosyltransferases . We show that the compounds identified in the donor-displacement screen of MurG are selective for MurG over other enzymes that use similar or identical substrates, including structurally related enzymes . The donor displacement assay described here should be adaptable to many other NDP-Gtfs and represents a new strategy to identify selective NDP-Gtf inhibitors.

Am Surg, 2004 May, 70(5), 467 - 71
Reducing medication errors in a surgical residency training program; Larson KA et al.; Medication errors contribute to in-hospital morbidity and mortality . Teaching hospitals and the surgical residency training programs they support should take proactive steps to reduce error frequency . In order to accomplish meaningful error reduction, we must first define the scope and nature of the problem . Pharmacists at the Monmouth Medical Center prospectively recorded medication prescribing errors made by surgical residents during 2 years . These data were reviewed to determine the types of medication errors made most frequently by surgical house officers . Seventy-five medication-prescribing errors were made by surgical house staff in the years 2001 and 2002 . Thirty-three of these errors involved orders for antibiotic therapy . Errors that could not be directly attributed to knowledge deficits were responsible for 36 of the 75 errors (48%), whereas specific knowledge deficits were responsible for 39 of the 75 errors (52%) . Twentyeight of the 36 errors not directly attributable to knowledge deficits (78%) were made at the postgraduate year one level, whereas only 15 of the 39 knowledge deficit errors (38%) were made at the postgraduate year one level . Though targeted education to address specific knowledge deficits may substantially reduce the occurrence of "knowledge deficit" medication errors within surgical residency training programs, more costly measures such as the implementation of physician computerized order entry will likely be needed to reduce maximally the frequency of medication ordering errors . Many prescribing errors cannot be attributed to specific knowledge deficits.

Clin Infect Dis, 2004 Jun 1, 38(11), 1586 - 91 Epub 2004 May 12.
The use and interpretation of quasi-experimental studies in infectious diseases; Harris AD et al.; Quasi-experimental study designs, sometimes called nonrandomized, pre-post-intervention study designs, are ubiquitous in the infectious diseases literature, particularly in the area of interventions aimed at decreasing the spread of antibiotic-resistant bacteria . Little has been written about the benefits and limitations of the quasi-experimental approach . This article outlines a hierarchy of quasi-experimental study design that is applicable to infectious diseases studies and that, if applied, may lead to sounder research and more-convincing causal links between infectious diseases interventions and outcomes.

Arch Dis Child, 2004 Jun, 89(6), 562 - 7
Lower respiratory tract illness and RSV prophylaxis in very premature infants; Lacaze-Masmonteil T et al.; AIMS: To determine the frequency of and the risk factors for readmissions for any lower respiratory tract illness (LRTI) and for respiratory syncytial virus (RSV) documented LRTI in children born very prematurely who had or had not received RSV prophylaxis . METHODS: Multicentre prospective longitudinal cohort study of 2813 infants, born between April 2000 and December 2000 at less than 33 weeks of gestational age, and followed until the end of the epidemic season . RESULTS: Among the 2256 children who had no bronchopulmonary dysplasia at 36 weeks of postmenstrual age and were not submitted to RSV prophylaxis, 27.4% were readmitted at least once for any reason during the epidemic season; 15.1% and 7.2% were readmitted at least once for any LRTI and RSV related LRTI, respectively . Children born at less than 31 weeks' gestation, having an intrauterine growth restriction, or living in a single mother family were at a significantly higher risk of readmission for LRTI in general as well as for RSV related LRTI . Of the 376 children submitted to prophylaxis, 28.2% were readmitted at least once for any LRTI and 6.1% for RSV related LRTI . CONCLUSION: One out of four children who had received no prophylaxis, was born very prematurely, and was without bronchopulmonary dysplasia at 36 weeks of postmenstrual age, was readmitted at least once for any reason . Roughly 50% and 20% of these readmissions were related to a LRTI and an RSV infection, respectively . Further epidemiological studies are warranted to assess the aetiology and impact of other respiratory pathogens on post-discharge readmission and respiratory morbidity in this population.

Antimicrob Agents Chemother, 2004 Jun, 48(6), 2228 - 32
Penetration of meropenem into pneumonic human lung tissue as measured by in vivo microdialysis; Tomaselli F et al.; Until recently, information on antibiotic pharmacokinetic properties in infected human lung tissue was limited . We therefore studied a microdialysis-based approach for measurement of the penetration of meropenem into the extracellular space fluid of human pneumonic lung parenchyma . The lung penetration of meropenem was determined for seven patients with pneumonia and metapneumonic pleural empyema treated by decortication . Intraoperatively, two microdialysis probes were inserted into pneumonic lung tissue and one was inserted into healthy skeletal muscle for reference values . Serum and microdialysis samples were collected at 20-min intervals for at least 8 h following a single intravenous dose of 1 g of meropenem . The maximum free interstitial concentration (mean and standard deviation) of meropenem in infected lung tissue was 11.4 +/- 10.9 mg/liter, and that in serum was 47.3 +/- 21.0 mg/liter . The areas under the curve for infected lung tissue (36.2 +/- 17.9 mg . h/liter) and serum (95.4 +/- 46.6 mg . h/liter) revealed a significant difference . This technique enabled quasi-continuous tissue pharmacokinetic measurements of free, unbound antibiotic in pneumonic lung tissue of patients with pneumonia . The present data corroborate the use of meropenem in the treatment of lung infections caused by extracellular bacteria, demonstrating the excellent distribution profile for meropenem in the interstitial space of human pneumonic lung tissue.

J Econ Entomol, 2004 Apr, 97(2), 646 - 53
Aphid (Hemiptera: Aphididae) resistance in wheat near-isogenic lines; Wang T et al.; Plant and aphid biomass, photosynthetic pigment (chlorophylls a and b and carotenoids) concentrations, and chlorophyll a/b and chlorophyll/carotenoid ratios were quantified in aphid-infested 'Tugela' near-isogenic lines (Tugela, Tugela-Dn1, Tugela-Dn2, and Tugela-Dn5) . The objectives were to quantify changes of photosynthetic pigments (chlorophylls a and b, and carotenoids) caused by aphid feeding and assess resistance of wheat isolines through aphid and plant biomass analysis . Biomass of bird cherry-oat aphid, Rhopalosiphum padi (L.) (Hemiptera: Aphididae)-infested plants was lower than Russian wheat aphid, Diuraphis noxia (Mordvilko) (Hemiptera: Aphididae),- infested plants . When infested by D . noxia, all lines showed increased biomass over time, except Tugela where biomass decreased on day 12 . No difference in plant biomass was detected among R . padi-infested and uninfested wheat lines . Biomass of D . noxia from Tugela (D . noxia-susceptible) was significantly higher than from plants with Diuraphis noxia-resistant Dn genes . Diuraphis noxia biomass from Tugela-Dn1 and Dn2 lines was not different from each other, but they were lower than from Tugela-Dn5 . In contrast, there was no difference in R . padi biomass among wheat lines . Concentrations of chlorophylls a and b and carotenoids were significantly lower in D . noxia-infested plants compared with R . padi-infested and uninfested plants . When infested by D . noxia, chlorophyll a and b concentrations were not different among wheat lines on day 3, but they were lower in Tugela and Tugela-Dn1 than in Tugela-Dn2 and -Dn5 plants on days 6 and 12 . However, no difference was detected in chlorophyll a/b or chlorophyll/carotenoid ratio among Tugela lines . The study demonstrated that Dn genes in the Tugela isolines conferred resistance to D . noxia but not to R . padi . Tugela-Dn1 was antibiotic, Tugela-Dn2 was tolerant and antibiotic, and Tugela-Dn5 was moderately antibiotic.

Crit Care, 2004 Jun, 8(3), 157 - 62 Epub 2003 Sep 29.
Clinical review: new technologies for prevention of intravascular catheter-related infections; Cicalini S et al.; Intravascular catheters have become essential devices for the management of critically and chronically ill patients . However, their use is often associated with serious infectious complications, mostly catheter-related bloodstream infection (CRBSI), resulting in significant morbidity, increased duration of hospitalization, and additional medical costs . The majority of CRBSIs are associated with central venous catheters (CVCs), and the relative risk for CRBSI is significantly greater with CVCs than with peripheral venous catheters . However, most CVC-related infections are preventable, and different measures have been implemented to reduce the risk for CRBSI, including maximal barrier precautions during catheter insertion, catheter site maintenance, and hub handling . The focus of the present review is on new technologies for preventing infections that are directed at CVCs . New preventive strategies that have been shown to be effective in reducing risk for CRBSI, including the use of catheters and dressings impregnated with antiseptics or antibiotics, the use of new hub models, and the use of antibiotic lock solutions, are briefly described.

J Ky Med Assoc, 2004 May, 102(5), 209 - 14
Rocky Mountain spotted fever at Koair Children's Hospital, 1990-2002; Hayden AM et al.; The reported average annual incidence of Rocky Mountain spotted fever (RMSF) in Kentucky is less than 5 per million population, although seroprevalence studies suggest that exposure to Rickettsia riskettsii, the causative agent, is relatively common among children . The experience with RMSF at Kosair Children's Hospital over a 12-year period was reviewed . Fifteen cases were identified (5 boys and 10 girls) . Illness onset ranged from April to October, and 4 patients resided in Jefferson County . The classic triad of fever, rash, and headache was present in only 60% of cases, and tick attachment was reported in only 40% . On average, 6 days elapsed from onset of symptoms to initiation of appropriate antibiotic therapy . One patient suffered splenic infarction and necrosis of the digits due to shock and disseminated intravascular coagulopathy, and 2 patients died . RMSF is a significant cause of pediatric morbidity and mortality in this region of Kentucky . Affected children may reside in relatively urban parts of the state . Initial clinical features may be nonspecific . This, as well as decreased awareness of disease and (unjustified) reluctance to use doxycycline may contribute to delays in initiating therapy.

Acta Chir Orthop Traumatol Cech, 2004, 71(2), 73 - 9
{A cannulated articulating spacer--a functional implant for treatment of infected hip joint prostheses}; Jahoda D et al.; PURPOSE OF THE STUDY: Two-stage revision arthroplasty with the use of a spacer is generally accepted as a reliable method for treating infected hip replacements . Spacers made from antibiotic-loaded bone cement give good results in treatment of deep infections, but this technique is demanding in terms of spacer shaping . In addition, the conventional spacer may dislocate or fracture during patient mobilization . We attempted to avoid the disadvantages of conventional spacers by the construction of a cannulated articulating spacer . This is a special implant consisting of a polyethylene acetabulum, a stem, a modular neck and a head . Both the acetabulum and stem are covered with antibiotic-impregnated bone cement . They are subsequently pressed into the bone bed to make impression in the cement . The union of the bone bed with cement, which occurs in conventional implantation, must be avoided . This is achieved by making movements with the implant attached to an insertion handle, and by irrigating the operative field with large volumes of saline . A drain inserted in the canal running along the stem long axis facilitates continuous lavage of the medullary cavity . MATERIAL AND METHODS: A total of 11 patients with deep infection of a hip replacement were treated with the use of a cannulated articulating spacer in the years 2002 and 2003 . Seven patients had late hematogenous infections and four had chronic delayed infections . The drains providing lavage stayed in place for about 10 to 12 days or less when three consecutive cultivations of drainage discharge were negative . Antibiotics were administered for at least 6 weeks according to the results of CRP and FW assessment . The reimplantation was planned on the basis of laboratory and clinical findings . The outcome was evaluated using the Harris hip score . RESULTS: Infection was successfully eradicated in all cases . The average time during which the cannulated articulating spacer was in place was 9.4 weeks . The results, as rated by the Harris hip score, were very good; after reimplantation, the average score was 95.1 points (range, 92 to 99) . Even better evidence of the advantages of this method was provided by the increase in the average Harris hip score, which was 35.3 points (range, 26 to 69) . No spacer dislocation or any other mechanical complication associated with the implant were recorded . DISCUSSION: Our results achieved with the cannulated articulating spacers developed in our department, as compared with conventional ones, show that the articulating spacer provides the patient with greater comfort and, therefore, improved quality of life for the period between the removal of a loose prosthesis and reimplantation of a definitive one . This method markedly reduces the risk of failure or dislocation of the temporary implant . In comparison with the PROSTALAC system, which is difficult to obtain and which requires complicated instrumentation, our method is simpler and less expensive . Our results show that the presence of an articulating spacer as a foreign body has no effect on the efficacy of treatment for deep infection . CONCLUSIONS: The procedure for preparing a cannulated articulating spacer described here is a modification of the method used to treat deep infection at the site of a total hip arthroplasty; it is inexpensive and provides markedly greater comfort for the patient . The technique combines the advantages of a two-stage revision involving spacer insertion with the use of lavage . Because patient have no major complaint and there is low risk of implant failure, the method allows us to adjust the reimplantation timing to the course of infection eradication and patients' overall health status.

Kyobu Geka, 2004 May, 57(5), 403 - 6
{Infected thoracoabdominal aortic aneurysm; report of a case}; Takeda T et al.; A 54-year-old man complained of pain in the left upper abdomen with fever . His past medical history was significant for non-insulin-dependent diabetes mellitus and hypertension . Leucocytosis and an elevation of CRP levels were detected . Thoracoabdominal aneurysm of 69 mm in diameter was identified by enhanced computed tomography (CT) . An infected thoracoabdominal aortic aneurysm was diagnosed and an emergency operation was performed . The aneurysm was treated by debridement of the infected aortic tissue and in situ prosthetic graft replacement followed by antibiotic therapy . The postoperative course was uneventful and there were no adverse neurological symptoms . After surgery, antibiotics were administered for 1 month intravenously and the patient was discharged on oral antibiotics for 2 months after the operation . The patient is doing well 7 months after the operation.

Diabetes Metab Res Rev, 2004 May-Jun, 20 Suppl 1, S56 - 64
Diagnosing and treating diabetic foot infections; Lipsky BA et al.; Foot infections are a common, complex and costly complication of diabetes . We have made considerable progress in establishing consensus definitions for defining infection . Similarly, we have learned much about the appropriate ways to diagnose both soft tissue and bone infections . Accompanying these advances have been improvements in our knowledge of the proper approaches to antibiotic (and surgical) therapy for diabetic foot infections . Furthermore, investigators have explored the value of various adjunctive therapies, especially granulocyte colony stimulating factors and hyperbaric oxygen, for improving outcomes . This paper presents a summary of a minisymposium on infection of the diabetic foot that was held at the fourth International Symposium on the Diabetic Foot, in Noordwijkerhout, The Netherlands . Crown copyright 2004 . Reproduced with the permission of Her Majesty's Stationery Office . Published by John Wiley & Sons, Ltd.

J Contemp Dent Pract, 2004 May 15, 5(2), 70 - 80
Dental management of the Down and Eisenmenger syndrome patient; Chung EM et al.; About 40% to 50% of Down syndrome (DS) patients can have significant congenital heart defects such as patent ductus arteriosus, Tetralogy of Fallot, and septal defects . Patients with large septal defects may develop Eisenmenger syndrome (ES), which is defined by the cardiac septal defect and pulmonary hypertension coupled with a reverse right to left shunting of blood flow . DS patients that suffer from this condition require special considerations in the delivery of their dental care to prevent further medical complications or emergencies such as infection, cyanotic episodes, and thromboemboli . Collaboration with the cardiologist is also essential to ensure a complete and comprehensive pre-operative work up . The purpose of this article is to describe the dental management of DS patients with ES under general anesthesia.

J Bacteriol, 2004 Jun, 186(11), 3570 - 7
Novel genes that influence development in Streptomyces coelicolor; Gehring AM et al.; Filamentous soil bacteria of the genus Streptomyces carry out complex developmental cycles that result in sporulation and production of numerous secondary metabolites with pharmaceutically important activities . To further characterize the molecular basis of these developmental events, we screened for mutants of Streptomyces coelicolor that exhibit aberrant morphological differentiation and/or secondary metabolite production . On the basis of this screening analysis and the subsequent complementation analysis of the mutants obtained we assigned developmental roles to a gene involved in methionine biosynthesis (metH) and two previously uncharacterized genes (SCO6938 and SCO2525) and we reidentified two previously described developmental genes (bldA and bldM) . In contrast to most previously studied genes involved in development, the genes newly identified in the present study all appear to encode biosynthetic enzymes instead of regulatory proteins . The MetH methionine synthase appears to be required for conversion of aerial hyphae into chains of spores, SCO6938 is a probable acyl coenzyme A dehydrogenase that contributes to the proper timing of aerial mycelium formation and antibiotic production, and SCO2525 is a putative methyltransferase that influences various aspects of colony growth and development.

AJR Am J Roentgenol, 2004 Jun, 182(6), 1443 - 9
Conventional open surgery versus percutaneous catheter drainage in the treatment of cervical necrotizing fasciitis and descending necrotizing mediastinitis; Nakamori Y et al.; OBJECTIVE: The purpose of our study was to determine the clinical usefulness of percutaneous catheter drainage compared with conventional surgical drainage for cervical necrotizing fasciitis and descending necrotizing mediastinitis . SUBJECTS AND METHODS . Thirty-one patients with cervical necrotizing fasciitis and descending necrotizing mediastinitis were included . Twenty consecutive patients were treated by percutaneous catheter drainage . Catheters were introduced into the infected space from the neck, under the guidance of sonography and X-ray fluoroscopy . The results of the treatment were compared with those of 11 patients treated previously by surgical drainage . RESULTS: In the catheter group, no patient required supplementary surgical drainage . Mortality was 0% in both groups . Comparison of length of stay in the ICU, serial changes in C-reactive protein levels, duration of antibiotic therapy, and duration of mechanical ventilation all showed no statistically significant difference between groups . Secondary infection of the wound and positive culture of antibiotic-resistant bacteria were observed less frequently in the catheter group than in the open surgical group . The total use of plasma infusion and analgesics was significantly less in the catheter group than in the surgery group . Oral feeding was started significantly earlier in the catheter group than in the surgery group . CONCLUSION: Percutaneous catheter drainage for cervical necrotizing fasciitis and descending necrotizing mediastinitis was less invasive than conventional surgical drainage but produced a similar outcome.

Br J Dermatol, 2004 May, 150(5), 958 - 65
Human T-cell leukaemia/lymphoma virus type 1-associated infective dermatitis in Africa: a report of five cases from Senegal; Mahe A et al.; BACKGROUND: Infective dermatitis (ID) is a rare dermatological condition of childhood that has been linked to human T-cell leukaemia/lymphoma virus type 1 (HTLV-1) . Most cases have been reported in the Caribbean . Although several million people are estimated to be infected by HTLV-1 in sub-Saharan Africa, no case of ID has been reported in this area . OBJECTIVES: To identify and to describe cases of HTLV-1-associated ID in Senegal, West Africa . METHODS: Over a 3-year period, a serological test for HTLV-1 was performed at a dermatological centre in Dakar, Senegal, in children who presented with a picture suggestive of ID . Complementary haematological, immunological and virological investigations were performed in infected children and in their mothers . RESULTS: Five patients with typical HTLV-1-associated ID were identified, of ages 17, 5, 4, 3 and 3 years; two patients belonged to the same family . They all presented with repeated flares of superinfected dermatitis involving typical sites of ID (mainly the scalp, external ears, nares and eyelids), associated with nasal discharge, and less commonly with a nonspecific papular rash on the face or trunk . Although oral antibiotic therapy always gave effective control of the symptoms, recurrences were constant . A persisting dry dermatitis of the retroauricular folds was common between flares . Infection in the oldest patient was associated with a chronic adult T-cell leukaemia/lymphoma . The mothers of three patients, and the grandmother of another, were all infected by HTLV-1 strains belonging to the Cosmopolitan molecular subtype, with a perfect nucleotide identity of long-terminal repeat and env gp21 genomic regions within each family . CONCLUSIONS: We present the clinical and virological features of the first reported African cases of HTLV-1-associated ID . When compared with data from the Caribbean, infectious features seemed particularly prominent . ID appears to be overlooked in sub-Saharan Africa, where it might be easily confused with common pyoderma . Breast feeding appears to be the origin of HTLV-1 contamination of the children.

Br J Plast Surg, 2004 Jun, 57(4), 303 - 10
Pulsed dye laser therapy for rosacea; Tan ST et al.; Rosacea is a chronic and progressive inflammatory skin disorder affecting the facial convexities for which no curative measure is currently available . Forty consecutive patients with rosacea were treated with the Cynosure PhotoGenica V pulsed dye laser . The improvement following laser therapy was assessed according to a sliding scale: 1 (worse after treatment), 2 (no improvement), 3 (slight improvement), 4 (moderate improvement), 5 (marked improvement) . Following an average of 2.4 (range 1-10) laser treatments, a mean score of 4.4 and 4.3 for overall improvement was achieved as judged by the patients and independently assessed by a family member or a close friend of the patients, respectively . The response of erythema and telangiectasia to laser therapy, evaluated by an independent panel of 10 members, showed a mean score of 3.7 . Three patients experienced an exacerbation of rosacea during the treatment period requiring antibiotic therapy . During the follow-up period of 6.0-55.5 (mean, 23.3) months after completion of laser therapy, no patient (including 13 patients in whom papulation and pustulation which were amongst the presenting symptoms) required medical treatment . Six patients developed post-inflammatory hyper-pigmentation necessitating skin bleach but no other complication such as scarring was observed . Three patients reported that the residual erythema had progressed after an initial improvement during follow-up periods of 52.4, 15.8 and 6.0 months . All patients felt that laser therapy was worthwhile . We conclude that pulsed dye laser therapy is a useful treatment for rosacea.

Veterinary Clin North Am Exot Anim Pract, 2004 May, 7(2), 351 - 73, vii
Guinea pig and chinchilla care and husbandry; Donnelly TM et al.; This article reviews breeds and coat colors of guinea pigs and chinchillas, their husbandry, care and anatomy . The unusual reproductive physiology and reproductive diseases of these animals are described . We cover nutrition, the potential for disease on poor diets, and the vocalization of hystricomorph rodents . Skills such as handling, sexing, blood collection and drug administration, including antibiotic toxicity are described . The conclusion lists recommended textbooks, pet owner manuals, and websites.

Anal Chem, 2004 May 15, 76(10), 2807 - 12
In situ investigation of drug diffusion in hydrogels by the refractive index method; Weng L et al.; This work describes a simple but novel analytical method for in situ monitoring of the diffusion process of drugs in hydrogels based on refractive index measurements . The diffusion process was monitored by recording the refraction of a laser beam passing through a triangular cell, which allows the determination of changes in the refractive index distribution from the deviated distance of the linear beam . Compared to conventional methods, this new method exhibits advantages such as more simplicity, lower cost, and speed . Further, the refractive index method permits the determination of the concentration distribution of solutes in the hydrogels at any time during the diffusion process under nondestructive circumstances . The precision was determined by successfully applying this new method to the diffusion of a typical antibiotic drug, cefazolin sodium, in agarose gels of various concentrations . By employing Fick's second law, the diffusion behavior was investigated and the diffusion coefficients of cefazolin sodium in agarose gels were therefore obtained . Amsden's physical model based on obstruction effect was applied to the simulation of the diffusion process of cefazolin sodium and turned out to fit the results quite well.

Tuberk Toraks, 2003, 51(3), 325 - 32
{Nebuliser therapy}; Demir G et al.; We use the nebuliser therapy to achieve rapid improvement in patients with acute airway limitation . Besides, this drug is effective in asthmatic children, in elderly patients and in patients with end-stage disease who need palliative care . Nowadays nebuliser therapy is used not only for bronchodilatation but also for antibiotic and expectoration treatment . Although nebuliser therapy provides a rapid and effective treatment in airway limitation, the patients who receive home nebuliser therapy may suffer from severe and incurable infections if the hygienic conditions are not achieved . Therefore, the indications of nebuliser therapy should be precisely determined and special care should be given in the choice of the patients who will receive nebuliser therapy.

Singapore Med J, 2004 May, 45(5), 229 - 31
Piriformis pyomyositis: a rare cause of sciatica; Chong KW et al.; A 30-year-old Thai woman with piriformis pyomyositis presented with sciatica . Computed tomography showed swelling and enhancement of the right gluteus medius and piriformis muscles . She made a complete recovery after a course of intravenous antibiotics . This condition has only been reported three other times and is often diagnosed with difficulty . It could be erroneously dismissed as a lumbar disc prolapse . If untreated, it could lead to prolonged hospital stay and death . A high index of suspicion, early diagnosis and appropriate antibiotic or surgical treatment leads to full recovery.

Bioorg Med Chem, 2004 Jun 1, 12(11), 3063 - 8
Nonbonded bivalence approach to cell-permeable molecules that target DNA sequences; Pang YP; Polyamides such as the natural antibiotic distamycin A can form binary or ternary complexes with B-DNA . The driving forces and advantages for forming the ternary complexes are not fully understood . The computational studies reported herein suggest that three- and four-ring polyamides have a propensity for forming the same dimer conformations in water as those in their ternary complexes . The pre-dimerization of a polyamide in water facilitates the formation of the ternary complex, making the polyamide more selective, and tighter binding to the minor groove whose minimal width is predetermined by the B-DNA sequence . Relative to the dimer tethered with covalent bonds, the smaller, monomeric polyamide available from reversible dimerization in water makes the molecule inherently more cell permeable . A nonbonded bivalence approach that dimerizes molecules by intermolecular interactions is proposed for improving affinity, selectivity, and cell permeability.

J Oral Sci, 2004 Mar, 46(1), 25 - 35
A comparative evaluation of the clinical effects of systemic and local doxycycline in the treatment of chronic periodontitis; Akalin FA et al.; In this study, the clinical efficacies of systemic doxycycline (SD) and local doxycycline (LD) in the treatment of chronic periodontitis were compared . Forty-five patients were studied in 3 main groups with 5 treatments: SD alone, SD+scaling-root planing (SD+SRP), LD alone, LD+SRP and SRP alone . Antibiotic-treated patients were given doxycycline treatment alone in 1 quadrant of their upper jaws, and doxycycline+SRP was given in the contralateral quadrant . The areas included at least 4 teeth with > or = 5 mm pockets . Probing depth (PD), clinical attachment level, gingival index, sulcular bleeding index and plaque index values were recorded at baseline and the 7th week . The results were statistically analyzed . All of the clinical parameters were significantly reduced by all treatments (P < or = 0.05) . The SD and LD treatments alone provided significant clinical healings . The significant differences among the groups were only in PD at the 7th week . The LD treatment provided significantly higher PD reduction than the SD treatment (P < or = 0.05) . No significant difference was found between the SD+SRP and the LD+SRP treatments . There was no significant difference between SD+SRP and SRP alone treatment (P > 0.05) . The SD group showed lower PD reduction than SRP group (P < or = 0.05), while no significant difference was found between LD and SRP treatments . The LD alone treatment seemed more effective than SD alone treatment on PD reduction, but no significant difference was found between them when combined with the SRP . LD may be more preferable than SD as an adjunct to mechanical treatment since LD seems more effective than SD on PD reduction and does not have the side effects of SD.

Plant Physiol, 2004 May, 135(1), 39 - 46
High-frequency transformation of undeveloped plastids in tobacco suspension cells; Langbecker CL et al.; Although leaf chloroplast transformation technology was developed more than a decade ago, no reports exist of stable transformation of undeveloped plastids or other specialized plastid types, such as proplastids, etioplasts, or amyloplasts . In this work we report development of a dark-grown tobacco suspension cell model system to investigate the transformation potential of undeveloped plastids . Electron microscope analysis confirmed that the suspension cells carry plastids that are significantly smaller (approximately 50-fold less in volume) and have a very different subcellular localization and developmental state than leaf cell chloroplasts . Using antibiotic selection in the light, we demonstrated that both plastid and nuclear transformation of these cell suspensions is efficient and reproducible, with plastid transformation frequency at least equal to that of leaf chloroplast transformation . Homoplasmic plastid transformants are readily obtained in cell colonies, or in regenerated plants, providing a more consistent and versatile model than the leaf transformation system . Because of the uniformity of the cell suspension model, we could further show that growth rate, selection scheme, particle size, and DNA amount influence the frequency of transformation . Our results indicate that the rate-limiting steps for nuclear and plastid transformation are different, and each must be optimized separately . The suspension cell system will be useful as a model for understanding transformation in those plant species that utilize dark-grown embryogenic cultures and for characterizing the steps that lead to homoplasmic plastid transformation.

Mol Cancer Ther, 2004 May, 3(5), 551 - 66
Simultaneous inhibition of hsp 90 and the proteasome promotes protein ubiquitination, causes endoplasmic reticulum-derived cytosolic vacuolization, and enhances antitumor activity; Mimnaugh EG et al.; The ansamycin antibiotic, geldanamycin, targets the hsp 90 protein chaperone and promotes ubiquitin-dependent proteasomal degradation of its numerous client proteins . Bortezomib is a specific and potent proteasome inhibitor . Both bortezomib and the geldanamycin analogue, 17-N-allylamino-17-demethoxy geldanamycin, are in separate clinical trials as new anticancer drugs . We hypothesized that destabilization of hsp 90 client proteins with geldanamycin, while blocking their degradation with bortezomib, would promote the accumulation of aggregated, ubiquitinated, and potentially cytotoxic proteins . Indeed, geldanamycin plus bortezomib inhibited MCF-7 tumor cell proliferation significantly more than either drug alone . Importantly, while control cells were unaffected, human papillomavirus E6 and E7 transformed fibroblasts were selectively sensitive to geldanamycin plus bortezomib . Geldanamycin alone slightly increased protein ubiquitination, but when geldanamycin was combined with bortezomib, protein ubiquitination was massively increased, beyond the amount stabilized by bortezomib alone . In geldanamycin plus bortezomib-treated cells, ubiquitinated proteins were mostly detergent insoluble, indicating that they were aggregated . Individually, both geldanamycin and bortezomib induced hsp 90, hsp 70, and GRP78 stress proteins, but the drug combination superinduced these chaperones and caused them to become detergent insoluble . Geldanamycin plus bortezomib also induced the formation of abundant, perinuclear vacuoles, which were neither lysosomes nor autophagosomes and did not contain engulfed cytosolic ubiquitin or hsp 70 . Fluorescence marker experiments indicated that these vacuoles were endoplasmic reticulum derived and that their formation was prevented by cycloheximide, suggesting a role for protein synthesis in their genesis . These observations support a mechanism whereby the geldanamycin plus bortezomib combination simultaneously disrupts hsp 90 and proteasome function, promotes the accumulation of aggregated, ubiquitinated proteins, and results in enhanced antitumor activity.

AJNR Am J Neuroradiol, 2004 May, 25(5), 873 - 5
Spontaneous sphenoid sinus mucocele revealed by meningitis and brain abscess in a 12-year-old child; Malard O et al.; Sphenoid sinus mucocele is an uncommon lesion related to inflammatory disease that is diagnosed after surgery or a traumatic event . This report describes an unusual case revealed by bacterial meningitis and cerebral abscess in a 12-year-old child . CT and MR imaging allowed precise extension to the skull base in preoperative management and follow-up investigations . Endoscopic transnasal marsupialisation of the mucocele and antibiotic therapy led to complete remission . There was no evidence of recurrence after 6 months, which suggests that sphenoid mucoceles, regardless of size and complications, can be treated by endoscopic sinus surgery.

Ann Ital Chir, 2003 Sep-Oct, 74(5), 559 - 63
{Pilonidal sinus: an retrospective analysis of 205 cases}; Castronovo G et al.; Sinus pilonidalis or the sacrococcigea cyst, normally is considered a "small surgical pathology" and actually it is controversial disease regarding its pathogenesis and treatment . Today the congenital hypothesis of this pathology is not considered . The etiopathogenesis exclude vestigia embryonic origin and consider it an inflammatory disease . Traumatism of the sacral region, hirsutism, hormonal secretion stimulating, and furrow sacral furrow cutaneous, explain the prevalence of this pathology in the male sex and in the puberale age . It usually appears after the puberta and extension one various frequency of presentation in males sex (1.3%) regarding females (0.11%) . The symptomatology can be rare or introduce itself in violent and intense way with on abscess of the region, or with only or multiple fistulas orifices from which exit materialclarly purulent . Normally cystic cavity is one, situated in the subcutaneous tissue with annexed inflammatory phenomena . This cavity to times communicates with the skyn fistulating . The treatment of election is surgical and must weighted and be regulated in relation to the entity of the lesion and its inflammatory picture . Sometimes the medical therapy with anti-inflammatory and antibiotic is not control the symptomatology and it need the surgical treatment.

J Integr Neurosci, 2004 Mar, 3(1), 3 - 6
Is it possible to restore function with two percent surviving neural tissue?
Bach-Y-Rita P.
How much surviving normal neural tissue is required for functional reorganization after a lesion? Clinical and experimental studies suggest that at little as two percent remaining tissue may be sufficient, at least in some cases, for functional reorganization . Recent sensory substitution studies with persons who have been diagnosed with total vestibular loss (e.g., due to an ototoxic reaction to an antibiotic) suggest that the persisting function after removal of the substitution system may be related to the survival of a small amount of vestibular tissue.

Childs Nerv Syst, 2004 Jul, 20(7), 468 - 72
Cerebral toxocariasis: a possible cause of epileptic seizure in children; Bachli H et al.; INTRODUCTION: Toxocariasis is a worldwide human helminthiasis, which is mostly asymptomatic and caused by toxocara canis, a roundworm in dogs . These can cause visceral larva migrans syndrome in humans who ingest contaminated soil . CNS manifestation with a focal mass lesion is very rare, seizures often being the first symptom . CASE REPORT: We describe an 11-year-old girl presenting with a generalized epileptic seizure and eosinophilia in blood . Under antibiotic therapy under the assumption of toxoplasmosis the lesion did not decrease and surgical resection was considered . We used computer-assisted surgery (CAS) for careful tissue resection . Postoperatively the diagnosis of toxocariasis was confirmed and albendozole medication was administered for 7 days . The patient developed well without neurological deficits or seizures . CONCLUSION: We conclude that although neurological involvement is rare in toxocariasis, a cerebral infection in a child with epileptic seizures and eosinophilia should be considered.

J Biol Chem, 2004 Jul 16, 279(29), 30106 - 13 Epub 2004 May 11.
The bacA gene of Escherichia coli encodes an undecaprenyl pyrophosphate phosphatase activity; El Ghachi M et al.; The bacA gene, the overexpression of which results in bacitracin resistance, was inactivated and shown to be non-essential for growth of Escherichia coli . It was proposed earlier that the bacA gene product may confer resistance to the antibiotic by phosphorylation of undecaprenol (Cain, B . D., Norton, P . J., Eubanks, W., Nick, H . S., and Allen, C . M . (1983) J . Bacteriol . 175, 3784-3789) . In the present work, this extremely hydrophobic membrane protein was overproduced and purified to near homogeneity . The analysis of its catalytic properties clearly demonstrated that the purified BacA protein exhibited undecaprenyl pyrophosphate phosphatase activity but not undecaprenol phosphokinase activity . This finding was perfectly consistent with the mechanism of action of bacitracin that consists in the sequestration of undecaprenyl pyrophosphate, the BacA enzyme substrate . The level of undecaprenyl pyrophosphate phosphatase was increased by 280-fold in cells carrying bacA on a multicopy expression plasmid . It was decreased by approximately 75% but was not completely abolished in a bacA disruption mutant, suggesting that BacA is the main E . coli undecaprenyl pyrophosphate phosphatase but that other protein(s) exhibiting such an activity should exist to account for the residual activity and viability of the mutant strain . This is the first gene encoding undecaprenyl pyrophosphate phosphatase identified to date . Considering its newly identified function, we propose to rename the bacA gene uppP.

Biopolymers, 2004 May-Jun 5, 74(1-2), 110 - 4
Intracellular uptake of modified oligonucleotide studied by two fluorescence techniques; Kocisova E et al.; Interaction, i.e., cellular uptake and intracellular distribution, of synthetic modified antisense oligonucleotide with the B16 melanoma cell line was studied using cationic polyene antibiotic, amphotericin B 3-dimethylaminopropyl amide, as a carrier vector . The antisense oligonucleotide--dT(15) oligomer analogue containing isopolar, nonisosteric, phosphonate-based internucleotide linkages 3'-O-P-CH(2)-O-5'--was labeled with fluorescent tetramethylrhodamine marker . The oligonucleotide itinerancy across the cell membrane and its distribution inside the cell was visualized using fluorescence microimaging . During the first several hours a strong preference staining of the cell nucleus was found . Fluorescence lifetime measurements from the intracellular environment (confocal laser microspectrofluorimeter, frequency domain phase/modulation technique in 1 to 200 MHz frequency region) yielded two spectral components of 4.9 and 1.4 ns lifetime, respectively . While the former component correlates with the previously characterized effect of the fluorophore binding to biomolecular targets in membranes and/or cytoplasm, the latter component is newly observed and its possible origin is discussed .

Curr Med Chem, 2004 May, 11(10), 1309 - 32
Chemistry and biology of cyclic depsipeptides of medicinal and biological interest; Sarabia F et al.; Cyclodepsipeptides comprise a wide variety of cyclic peptides of natural origin and are characterized by the occurrence of at least one ester linkage . The great interest that this class of natural products has elicited in scientific community is explained by their wide range of biological activities, intriguing mechanisms of action and attractive molecular architecture . For example, they display a variety of biological effects, such as immunosuppressant, antibiotic, antifungi, antiinflammatory or antitumoral activities . In addition, many of these cyclic depsipeptides represent useful tools for the research of biological processes involved in cellular regulation . The present review deals with the most interesting aspects of the biology and the chemistry of some of these compounds.

J Pak Med Assoc, 2004 Feb, 54(2), 88 - 95
Empirical treatment for tuberculosis: survey of cases treated over 2 years in a London area; Tariq SM et al.; OBJECTIVE: To determine factors influencing the decision to treat tuberculosis empirically and its outcome . METHODS: A retrospective survey was done to assess the factors influencing the decision to treat tuberculosis empirically and the effectiveness of such treatment, within a London area . Data on tuberculosis cases treated during 1995-96 (n = 218) was collected and analysed . RESULTS: One hundred and fifty-eight (72.5%) cases of tuberculosis were treated empirically, that is, in the absence of positive smear or histology . Factors suggesting tuberculosis were clinical suspicion, abnormal radiology, elevated Erythrocyte Sedimentation Rate (ESR) and/or C-reactive Protein (CRP), grade 3 or 4 Heaf test, contact or family history, and Heaf conversion . Significantly more Asian {79 of 105 (75.2%); p < 0.02} and African patients {61 of 81 (75.3%); p < 0.05} were treated empirically as compared to West European patients {14 of 28 (50%)} . Based on logistic regression, any non-European ethnicity carried a significant risk for being treated empirically {OR: 2.7, CI: 1.7-20.8; p < 0.05} . Patients requiring revision of diagnosis (n = 9) were older {55.7 +/- 10.1 vs 32.8 +/- 16.0 years; p < 0.001}; 6 of them had neoplastic conditions . CONCLUSION: In this survey, frequent use of empirical treatment for tuberculosis in non-European patients reflects the physicians' high index of suspicion . Although such therapy is justifiable in selected cases, the proportion requiring revision of diagnosis may be reduced by more thorough investigation, especially in older patients.

Am J Ther, 2004 May-Jun, 11(3), 218 - 28
Sirolimus-eluting coronary stents: novel devices for the management of coronary artery disease; Cheng-Lai A et al.; Despite major technological advances in the practice of percutaneous coronary intervention, restenosis of the treated arteries remains a challenge for many interventional cardiologists . Sirolimus is a macrolide antibiotic with potent antifungal, immunosuppressive, and antimitotic activities . Sirolimus inhibits in-stent restenosis via 2 major mechanisms of action: by blocking the process of neointimal hyperplasia by inhibiting smooth muscle cell proliferation and by inhibiting inflammatory cell activity . In pivotal clinical trials, the sirolimus-eluting stent has demonstrated significant improvements in angiographic and clinical outcomes compared with bare metal stents in patients with de novo lesions in native coronary arteries . Since the systemic exposure of sirolimus in patients who received the drug-eluting stent is minimal, adverse effects resulting from systemic exposure of sirolimus are unlikely to occur . Further studies are needed to determine the safety and effectiveness of sirolimus-eluting stents in patients with more complex coronary artery lesions . In addition, the long-term safety, efficacy, and cost-effectiveness of this novel drug-eluting device will need to be established in ongoing clinical trials . This review article focuses on the pharmacology as well as clinical studies of the sirolimus-eluting stent.

J Allergy Clin Immunol, 2004 May, 113(5), 902 - 9
Doxycycline reduces airway inflammation and hyperresponsiveness in a murine model of toluene diisocyanate-induced asthma; Lee KS et al.; BACKGROUND: Toluene diisocyanate (TDI) is a leading cause of occupational asthma . Although considerable controversy remains regarding its pathogenesis, TDI-induced asthma is an inflammatory disease of the airways characterized by airway remodeling caused, at least in part, by an excess of extracellular matrix deposition in the airway wall . Matrix metalloproteinases (MMPs) are major proteolytic enzymes that are involved in extracellular matrix turnover because of their ability to cleave all proteins constituting extracellular matrix . Previous studies have reported that MMP-9 might play a role in chronic airway inflammation and remodeling in asthma . OBJECTIVE: An aim of the current study was to evaluate the effects of MMP-inhibiting antibiotic, doxycycline, and MMP inhibitors on hyperresponsiveness and inflammation of the airways in TDI-induced asthma . METHODS: We used a murine model for TDI-induced asthma to examine the effect of doxycycline or MMP inhibitors on bronchial inflammation and airway hyperresponsiveness . RESULTS: The following typical pathophysiologic features are observed in the lungs of the mice: airway inflammation, airway hyperresponsiveness, and increased expression of MMP-9 mRNA and protein . Administration of doxycycline and MMP inhibitors reduced all of these pathophysiologic findings . In addition, the increased phosphorylated Akt but not Akt protein levels in lung tissues after TDI inhalation were significantly reduced by the administration of doxycycline and MMP inhibitors . CONCLUSION: These findings suggest that doxycycline may reduce airway inflammation and hyperresponsiveness through phosphatidylinositol 3-kinase pathway in a murine model of TDI-induced asthma.

J Womens Health (Larchmt), 2004 Apr, 13(3), 285 - 91
Adherence to oral therapies in pelvic inflammatory disease; Dunbar-Jacob J et al.; PURPOSE: To assess adherence to oral therapies in pelvic inflammatory disease (PID) . METHODS: Medication adherence to oral doxycycline therapy (100 mg) was measured using electronic event monitoring (EEM) among adult women with PID . Subjects (n = 91), who were predominantly black and with a high school or lower educational attainment, were randomly selected from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) Study, a trial in which subjects were randomized to either (1) . initial inpatient then outpatient or (2) . fully outpatient treatment with doxycycline and cefoxitin . Summary statistics calculated within treatment groups and in the cohort as a whole included the percentage of administrations taken, percentage of days with correct dosage, percentage of days with no drug taken, time elapsed until the first drug holiday, and percentage of optimal dosing intervals . RESULTS: Study subjects took an average of 70% of prescribed doses, took the prescribed two daily doses for less than half of their outpatient days, took an unscheduled drug holiday for almost 25% of their outpatient days, and took only 16.9% of their doses within the optimal timing interval . In general, working, not bleeding with sex, and not drinking hard liquor were positively associated with measures of adherence . Adherence estimates were similar among women in the inpatient and outpatient groups after hospital discharge . CONCLUSIONS: The disturbing rates of time interval adherence, even after hospitalization, suggest the need to determine the effectiveness of antibiotic regimens involving shorter courses and longer dosing intervals.

J Pak Med Assoc, 2004 Mar, 54(3), 133 - 4
Tropical sprue: revisited; Khokhar N et al.; OBJECTIVE: To review the experience of patients presenting with clinical manifestations of tropical sprue and assess their diagnosis and management, response to treatment and follow up . METHODS: This single center retrospective descriptive study was done at Shifa International Hospital, Islamabad from January 1994 to January 2003 . All patients who presented with diarrhea, anorexia, weight loss and anemia and who proved to have partial villous atrophy on intestinal biopsy and had responded to treatment with antibiotic and folic acid,were included in this review . RESULTS: A total of 42 patients were encountered during these years . There were 31 (74.0%) males and 11 (26%) females . The age ranged from 17-66 years . All patients presented with diarrhea, weight loss, anorexia and had megaloblastic anemia . In all patients, a distal duodenal biopsy showed partial villous atrophy . All were treated with tetracycline 1 g per day and folic acid 5 mg per day and responded to treatment within 4 weeks . Total treatment lasted 3 months and resulted in complete resolution of symptoms and gain of weight . The follow up lasted for a mean of 5 years and no relapses were noted . CONCLUSION: Tropical sprue presents with diarrhea, anorexia, weight loss, and megaloblastic anemia . The partial villous atrophy has been a constant finding . The response to treatment to tetracycline and folic acid has been uniformly successful.

Laryngoscope, 2004 May, 114(5), 923 - 30
Evaluation of the medical and surgical treatment of chronic rhinosinusitis: a prospective, randomised, controlled trial; Ragab SM et al.; OBJECTIVES: To conduct the first prospective, randomized, controlled trial evaluating and comparing the medical and surgical treatment of polypoid and nonpolypoid chronic rhinosinusitis (CRS) . MATERIALS AND METHODS: Ninety patients with CRS were equally randomized either to medical or surgical therapy . All patients underwent pre- and posttreatment assessments of visual analogue score (VAS), the Sinonasal Outcome Test-20 (SNOT-20), the Short Form 36 Health Survey (SF-36), nitric oxide (NO), acoustic rhinometry, saccharine clearance time (SCT), and nasal endoscopy . Each patient had three assessments: before starting the treatment, after 6 months, and, finally, after 1 year . RESULTS: Both the medical and surgical treatment of CRS significantly improved almost all the subjective and objective parameters of CRS (P <.01), with no significant difference being found between the medical and surgical groups (P >.05), except for the total nasal volume in CRS (P <.01) and CRS without polyposis (P <.01) groups, in which the surgical treatment demonstrated greater changes . CONCLUSION: CRS should be initially targeted with maximal medical therapy (e.g., a 3 month course of a macrolide antibiotic, douche, and topical steroid), with surgical treatment being reserved for cases refractory to medical therapy . The presence of nasal polyps is not a poor prognostic factor for the efficacy of CRS therapy, either surgical or medical.

Int J Pediatr Otorhinolaryngol, 2004 Jun, 68(6), 779 - 84
Current practice patterns in tonsillectomy and perioperative care; Krishna P et al.; OBJECTIVES: Tonsillectomy is one of the most commonly performed otolaryngologic procedures in the United States . Many options and controversies exist regarding techniques and peri-operative management . The purpose of the study was to examine current practice patterns among otolaryngologists regarding tonsillectomy . METHODS: A 13 question survey regarding tonsillectomy techniques and peri-operative management was mailed to 10% of randomly selected board certified otolaryngologists of the AAO-HNS in the spring of 2002 . Four hundred and eighteen anonymously completed questionnaires were returned, for a response rate of 58.5% . Statistical analysis of survey data was performed by means of cross tabulation and Pearson Chi-Square Calculation . RESULTS: Monopolar electrocautery was the most common technique used among those surveyed (53.5%) . There was a significant correlation between choice of monopolar electrocautery and the cited reason for choice of technique being decreased blood loss (P < 0.001) . There was no relationship between pediatric fellowship training and choice of technique . 97.7% routinely admitted sleep apnea patients for post-operative observation . There was no significant correlation between practice setting (tertiary versus community) and type of post-operative monitoring for sleep apnea patients, with patients most commonly admitted to an intermediate care setting . CONCLUSION: In our survey, the most common surgical technique for tonsillectomy was monopolar electrocautery, chosen for the reason of decreased blood loss.

East Afr Med J, 2004 Feb, Suppl, S33 - 40
Management of acute respiratory infections in drug shops and private pharmacies in Uganda: a study of counter attendants' knowledge and reported behaviour; Tumwikirize WA et al.; BACKGROUND: In Uganda, private pharmacies and drug shops are important sources of drugs for the majority of the population . In addition to selling drugs, these outlets often serve as primary sources of information about illness and drug therapy . However, the appropriateness of dispensing by staff in these drug outlets has been found to be suboptimal . Yet there has been no study documenting the determinants that underlie the dispensing pattern at these outlets . This study evaluated counter attendants' training background, their knowledge of acute respiratory infections (ARI), and their reported behaviour in the management of ARI in order to identify factors associated with dispensing behaviours . STUDY DESIGN AND SETTING: This descriptive study was conducted in Kampala District, Uganda and used a cross-sectional survey research design to analyse the practice of 197 drug outlets including 28 pharmacies and 169 drug stores . MAIN OUTCOME MEASURES: Counter attendants' training background; their knowledge of the causes, signs and symptoms of ARI; their perception of the dangers of ARI; and the drugs and advice offered for the management of mild and severe ARI . RESULTS: Majority of the counter attendants had medical or pharmacy training . Most of them were nurses . The attendants' workload was generally low . High levels of self-medication among clients were reported at the outlets . Staff at a management level had low knowledge of the aetiology, signs and symptoms, and dangers of ARI . Prescribing an antibiotic was found to be the usual practice for managing ARI cases . Counter attendants at those outlets seldom gave advice or referrals for ARI cases . In particular, patient demand was a main barrier to appropriate dispensing . Strategies suggested by attendants for improving rational dispensing were to educate the public, provide training for the attendants, and re-enforce government supervision of drug outlets . CONCLUSIONS: This study identified several self-reported inappropriate behaviours in the outlets . The formal training background and workload of counter attendants at drug shops and pharmacies were not found to be important contributors to irrational prescribing . The results of this study suggest that a combination of regulatory and educational interventions may yield to improvement in counter attendants' practices in private drug outlets.

East Afr Med J, 2004 Feb, Suppl, S25 - 32
Impact of a face-to-face educational intervention on improving the management of acute respiratory infections in private pharmacies and drug shops in Uganda; Tumwikirize WA et al.; BACKGROUND: In Uganda, although private retail pharmacies and drug shops are the most common sources of drugs for the majority of the population, the quality of care received from these outlets has been reported as suboptimal . It is believed that lack of adequate knowledge is an important underlying factor to such practices . OBJECTIVES: In this study, we investigated the impact of a face-to-face educational intervention on counter attendants' dispensing behaviour for mild and severe acute respiratory infections (ARI) in children at private pharmacies and drug shops . STUDY DESIGN AND SETTING: We used a quasi-experimental research design with comparison groups to analyse counter attendants' management of ARI before and after an intervention . The study was conducted in Kampala District, and used a sample of 191 registered drug outlets (27 pharmacies and 164 drug shops), stratified into two groups: 1) An experimental group that received training; 2) A control group unexposed to training . Data on the practices in the drug outlets from both groups were collected at two time-points: seven months before the intervention, and at one-month after the intervention . OUTCOME MEASURES: Two main outcome measures were considered: a) Assessment of the child's condition . b) The dispensing practices of counter attendants . RESULTS: The study found that despite the training, the assessment of the child's condition remained inadequate in both groups, where the child's age was the only question asked in more than 90% of cases . High levels of inappropriate dispensing practices for both mild and severe ARI were still persistent in both groups after the intervention . Antibiotic prescribing for both conditions was very common, and barely any advice or instruction was given with dispensed drugs . Client demand for particular drugs, competition among drug outlets, and inability of most clients to afford the recommended treatments were the main reported barriers that emerged from the focus group discussions with the counter attendants . CONCLUSIONS: The evaluation of the practices one month after the face-to-face educational intervention showed that the management of ARI did not improve in the drug outlets . While study design issues may have contributed to such findings, there are many other factors not related to knowledge and education that may indirectly hamper the promotion of appropriate dispensing in the private pharmacies and drug shops in Uganda . It is possible that a combination of interventions may contribute to improved management of ARI by counter attendants in the private drug shops and pharmacies in Uganda.

East Afr Med J, 2004 Feb, Suppl, S17 - 24
Impact of an educational intervention to improve prescribing by private physicians in Uganda; Obua C et al.; INTRODUCTION: Private physicians in urban Uganda treat a large percentage of common adult illnesses . Improving their prescribing would not only encourage more rational drug use, but also reduce costs to patients . Interventions to improve drug use are generally more successful when face-to-face educational methods are included . OBJECTIVES: To determine the effectiveness of a face-to-face educational intervention on the treatment of acute respiratory infections (ARI), malaria, and non-dysenteric diarrhoea by private physicians in three urban areas of Uganda . METHODS: The study used an intervention with comparison group design to evaluate the impact of the educational intervention . A total of 108 private physicians was divided into intervention (n = 30) and control (n = 78) groups . Surrogate patients, trained to simulate presenting symptoms and signs of the target conditions, were used to collect data on the medical practices and prescribing behaviours of the physicians . Intervention physicians were invited to a one-day interactive educational seminar facilitated by local opinion leaders that covered principles of rational drug use and the National Standard Treatment Guidelines for treating the target conditions . Physicians were also provided with data about baseline practices . RESULTS: Baseline data indicated high rates of inappropriate treatment practices by both intervention and control groups . There was nearly universal antibiotic use for ARI (over 90%), high rates of injections recommended for malaria (over 30%), and high rates of polypharmacy (over thee drugs per patient) . After the intervention, some significant improvements in key practices were observed in the intervention group . Compared to control physicians, antibiotic prescribing for ARI decreased by 23% in the intervention group, use of combination products for malaria declined by 28%, there were trends towards better adherence to guidelines for ARI and malaria, and marginal decreases in drug costs . However, the overall impacts of the intervention were limited, especially on quality indicators concerning history taking, adequate examination, and advice to patients . CONCLUSION: The face-to-face educational intervention resulted in some small improvements in key prescribing practices of private physicians . However, an intervention that involved repeated contacts with prescribers and which addressed economic considerations would be needed to obtain larger improvements . Private physicians need to be sensitized to and encouraged to use the National Standard Treatment Guidelines, and attempts to improve their prescribing should be supported by community education.

East Afr Med J, 2004 Feb, Suppl, S12 - 6
A comparison of prescribing practices between public and private sector physicians in Uganda; Ogwal-Okeng JW et al.; INTRODUCTION: Previous studies in the public sector in Uganda have demonstrated major prescribing problems due to polypharmacy and irrational use of antibiotics and injections . Little is known about prescribing in the private sector although there is little government regulation influencing practice in this sector . The introduction of policies such as the Uganda National Standard Treatment Guidelines (UNSTG) was expected to improve prescribing practices in the public and private sectors . This paper measures appropriateness of prescribing practices in the public and private sectors in Uganda for the treatment of Acute Respiratory Infections (ARI) and malaria in adult patients . DESIGN AND SAMPLING: We combined a prospective survey of treatment for simulated patients presenting with symptoms of malaria and ARI in 119 randomly selected private clinics and a retrospective survey of 600 prescription records for malaria and ARI (300 for each condition) randomly selected from 10 public health units in the Kampala, Masaka, and Jinja urban areas . OUTCOME MEASURES: Percentage of drug appropriately prescribed in each condition, % injection prescription, percentage antibiotic prescription, average number of drugs per case, average standardized cost per prescription, distribution of types of drugs prescribed . RESULTS: The overall appropriateness of prescribing for ARI and malaria was poor in both public and private sectors . Treatment of malaria was significantly less appropriate in the public sector compared to the private sector (14% vs . 27%, p = 0.002), with injectable chloroquine much more commonly prescribed . Prescribing of antibiotics for ARI was nearly universal in both sectors, with some prescriptions containing up to three antibiotics; newer, more expensive antibiotics were more commonly prescribed in the private sector . Polypharmacy and unnecessary prescribing of vitamins were common in both conditions and both sectors . CONCLUSIONS: Prescribing for adult malaria and ARI by both private and public practitioners did not conform to the UNSTGs . Although practitioners were largely the same in both sectors, prescribing practices often differed dramatically . The extent of inappropriate prescribing in both sectors calls for in-depth investigation of the system factors and motivations that underlie problem practices, and the development of interventions that target these causative factors.

J Biol Chem, 2004 Jul 9, 279(28), 28954 - 60 Epub 2004 Apr 28.
Conformation of membrane-associated proapoptotic tBid; Gong XM et al.; The proapoptotic Bcl-2 family protein Bid is cleaved by caspase-8 to release the C-terminal fragment tBid, which translocates to the outer mitochondrial membrane and induces massive cytochrome c release and cell death . In this study, we have characterized the conformation of tBid in lipid membrane environments, using NMR and CD spectroscopy with lipid micelle and lipid bilayer samples . In micelles, tBid adopts a unique helical conformation, and the solution NMR (1)H/(15)N HSQC spectra have a single well resolved resonance for each of the protein amide sites . In lipid bilayers, tBid associates with the membrane with its helices parallel to the membrane surface and without trans-membrane helix insertion, and the solid-state NMR (1)H/(15)N polarization inversion with spin exchange at the magic angle spectrum has all of the amide resonances centered at (15)N chemical shift (70-90 ppm) and (1)H-(15)N dipolar coupling (0-5 kHz) frequencies associated with NH bonds parallel to the bilayer surface, with no intensity at frequencies associated with NH bonds in trans-membrane helices . Thus, the cytotoxic activity of tBid at mitochondria may be similar to that observed for antibiotic polypeptides, which bind to the surface of bacterial membranes as amphipathic helices and destabilize the bilayer structure, promoting the leakage of cell contents.

Epilepsy Behav, 2004 Apr, 5(2), 151 - 8
Induction of audiogenic seizures in imipenem/cilastatin-treated rats; Zivanovic D et al.; We investigated the effect of intense audiogenic stimulation (AGS) on rats treated with the antibiotic imipenem and dipeptidase inhibitor cilastatin (Imi/Cil) . Under pentobarbital anesthesia (40 mg/kg) adult male Wistar rats were implanted with electrodes and cannulas were placed in the right lateral ventricle . Animals were divided into the following groups: (1) vehicle, (2) Imi/Cil 10 microg/10 microg, (3) Imi/Cil 25 microg/25 microg, (4) vehicle+AGS, (5) Imi/Cil 10 microg/10 microg +AGS, and (6) Imi/Cil 25 microg/25 microg +AGS . Imi/Cil was administered intracerebroventricularly in 5 microl of physiological saline . AGS (100+/-3 dB, 60 seconds) was applied at 15-minute intervals after the injection . Imi/Cil-induced seizures (twitching, forelimb clonus, headnodding, rearing, and clonic convulsions) and Imi/Cil-audio-induced seizures (wild running, clonic and tonic convulsions) were scored according to appropriate rating scales . Imi/Cil provoked convulsions dose-dependently . Each behavioral seizure response had a characteristic EEG correlate . AGS by itself did not provoke seizures in untreated rats . Sound stimulation in Imi/Cil-injected rats elicited typical audiogenic seizures, which were induced during five AGS tests (75 minutes postinjection) . In most cases audiogenic seizures were not associated with epileptiform activity in the EEG, indicating that spreading of seizures did not involve the cortex . Since Imi/Cil-induced and Imi/Cil-audio-induced seizures differed behaviorally and electroencephalographically, it is suggested that different neural pathways are responsible for these two types of seizures: neuronal networks in the cortex are involved in Imi/Cil-induced seizures, whereas audiogenic seizures use networks residing primarily in the brainstem.

J Biochem Mol Toxicol, 2004, 18(2), 69 - 77
Nitric oxide and oxidative stress in brain and heart of normal rats treated with doxorubicin: role of aminoguanidine; Abd El-Gawad HM et al.; Doxorubicin (DOX) is a potent antitumor antibiotic drug known to cause severe cardiac toxicity . Moreover, its adverse effects were found to be extended to the cerebral tissue . Several mechanisms for this toxicity have been ascribed . Currently, one of the most accepted mechanisms is through free radicals; however, the exact role of nitric oxide (NO) is still unclear . Accordingly, a NO-synthase inhibitor with some antioxidant property, aminoguanidine (AG), was selected to examine its potential protective effect against DOX-induced toxicity . Male Wistar albino rats (150-200 g) were allocated into a normal control group, DOX-induced toxicity group, and DOX + AG-treated group . DOX was injected i.p . at a dose of 10 mg/kg divided into four equal injections over a period of 2 weeks . AG was injected i.p . at a dose of 100 mg/kg 1 h before each DOX injection . The animals were sacrificed 24 h after the last DOX injection and the following parameters were measured: serum lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) activities, cardiac and cerebral contents of malondialdehyde (MDA), conjugated diene (CD), glutathione (GSH), NO, and cytosolic calcium, as well as superoxide dismutase (SOD) and glutathione peroxidase (GSHP(X)) activities . Cardiotoxicity was manifested by a marked increase in serum LDH and CPK in addition to the sharp increase in MDA reaching eightfolds the basal level . This was accompanied by significant increase in CD, NO, cytosolic calcium, SOD, and GSHP(X) content/activity by 69, 85, 76, 125, and 41% respectively as compared to normal control . On the other hand, GSH was significantly depressed . In brain, only significant increase in MDA and GSHP(X) and decrease in GSH were obtained but to a lesser extent than the cardiac tissue . AG treatment failed to prevent the excessive release of cardiac enzymes; however, it alleviated the adverse effects of DOX in heart . AG administration resulted in marked decrease in the elevated levels of MDA, NO, SOD, and GSHP(X), however, MDA level was still pathological . The altered parameters in brain were restored by AG . It is concluded that, AG could not provide complete protection against DOX-induced toxicity . Therefore, it is recommended that, maintenance of the endogenous antioxidant, GSH, and regulation of calcium homeostasis must be considered, rather than NO formation, to guard against DOX-induced toxicity .

J Oral Maxillofac Surg, 2004 May, 62(5), 527 - 34
Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases; Ruggiero SL et al.; PURPOSE: Bisphosphonates are widely used in the management of metastatic disease to the bone and in the treatment of osteoporosis . We were struck in the past 3 years with a cluster of patients with necrotic lesions in the jaw who shared 1 common clinical feature, that they had all received chronic bisphosphonate therapy . The necrosis that was detected was otherwise typical of osteoradionecrosis, an entity that we rarely encountered at our center, with less than 2 patients presenting with a similar manifestation per year . PATIENTS AND METHODS: We performed a retrospective chart review of patients who presented to our Oral Surgery service between February 2001 and November 2003 with the diagnosis of refractory osteomyelitis and a history of chronic bisphosphonate therapy . RESULTS: Sixty-three patients have been identified with such a diagnosis . Fifty-six patients had received intravenous bisphosphonates for at least 1 year and 7 patients were on chronic oral bisphosphonate therapy . The typical presenting lesions were either a nonhealing extraction socket or an exposed jawbone; both were refractory to conservative debridement and antibiotic therapy . Biopsy of these lesions showed no evidence of metastatic disease . The majority of these patients required surgical procedures to remove the involved bone . CONCLUSIONS: In view of the current trend of increasing and widespread use of chronic bisphosphonate therapy, our observation of an associated risk of osteonecrosis of the jaw should alert practitioners to monitor for this previously unrecognized potential complication . An early diagnosis might prevent or reduce the morbidity resulting from advanced destructive lesions of the jaw bone.

Photochem Photobiol Sci, 2004 May, 3(5), 423 - 9 Epub 2004 Feb 12.
Mechanistic aspects of Escherichia coli photodynamic inactivation by cationic tetra-meso(N-methylpyridyl)porphine; Salmon-Divon M et al.; The mechanistic aspects of Escherichia coli photodynamic inactivation (PDI) have been studied in bacteria expressing the reporter protein GFP, following transfection with wild type pGFP plasmid and treatment with the hydrophilic cationic sensitizer tetra-meso(N-methyl-4-pyridyl)porphine tetratosylate (TMPyP) . Cell survival and morphology during PDI were correlated with plasmid-GFP degradation in comparison to DNA and RNA strand-breaks, while photobleaching of the GFP chromophore was used to monitor protein photodamage . Singlet oxygen generated upon TMPyP photoactivation interacted with target nucleic acid polymers in a drug-and light-dose dependent manner . The hierarchy and cascade of the photodamage was in the order: genomic-DNA > total RNA > plasmid-DNA, as revealed by specific extraction and agarose electrophoresis . The notable resistance of the plasmid DNA in comparison to genomic DNA has implications for PDI of antibiotic-resistant bacteria . Re-growth of the treated cells in fresh medium showed structural features of an SOS response . Under these conditions, DNA repair machinery was initiated by typical alignment of DNA-protein co-aggregates accompanied by lateral assembly of ribosomes, apart from damaged DNA-arrays, as depicted by electron microscopy . GFP-TMPyP interactions were demonstrated by double green and red fluorescence on electrophoresis plates analyzed by spectral imaging . Photobleaching measurements revealed specific GFP photodamage directly related to PDI of the E . coli . The kinetics of both the GFP photobleaching and the K(+) efflux, representing photodamage to cytosolic proteins and membrane damage, respectively, were found to be similar . The survival curves were correlated to chromosomal degradation and ultrastructural damage . We conclude that TMPyP-dependent PDI of E . coli is primarily dependent on genomic DNA photodamage rather than on protein or membrane malfunctions.

Pediatrics, 2004 May, 113(5), 1352 - 6
Initial and follow-up costs by treatment outcome for children with respiratory infections; Howard DH et al.; OBJECTIVE: To estimate the initial and follow-up costs of treatment of respiratory infections among pediatric patients and the relationship between costs and outcomes . METHODS: A total of 3677 episodes of care from 2328 patients who were <17 years of age and had respiratory or ear infections that were treated with an antibiotic initially . The sample was drawn from the Medical Expenditure Panel Surveys for the years 1996 through 1999 . Treatment failure was defined as the receipt of a second antibiotic, different from the first, in a 4-week window . We compared follow-up costs by outcome (treatment failure vs success) using a 2-part model of medical costs . We also performed a paired analysis by selecting 2 episodes, one in which the outcome was failure and the other in which the outcome was success, for patients with at least 1 of each type and computing the difference in costs . RESULTS: Follow-up costs for provider visits for episodes for which the patient experienced treatment failure were 216 dollars versus 53 dollars for episodes for which the patient did not experience treatment failure . Follow-up drug costs, including the cost of the second antibiotic, were 75 dollars for children who experienced treatment failure versus 23 dollars, respectively . Cost estimates from the paired analysis were similar, confirming that results are not biased by unobserved time-invariant patient characteristics . CONCLUSION: Children who have respiratory infections and experience treatment failure incur substantially higher costs.

Pediatrics, 2004 May, 113(5), 1173 - 80
Are complete blood cell counts useful in the evaluation of asymptomatic neonates exposed to suspected chorioamnionitis?
Jackson GL, Engle WD, Sendelbach DM, Vedro DA, Josey S, Vinson J, Bryant C, Hahn G, Rosenfeld CR.
OBJECTIVE: Chorioamnionitis complicates 1% to 10% of pregnancies and increases the risk of neonatal infection . Women with chorioamnionitis receive intrapartum antibiotics, often resulting in inconclusive neonatal blood cultures . Peripheral neutrophil values are used frequently to assist in the diagnosis of neonatal infection and to determine duration of antibiotics; we sought to determine the utility of this approach . METHODS: A prospective observational study was performed in 856 near-term/term neonates who were exposed to suspected chorioamnionitis . Each received antibiotics for 48 hours unless clinical infection or positive blood cultures occurred . Peripheral neutrophils were measured serially and analyzed using the reference ranges of Manroe et al; an additional analysis of only the initial neutrophil values used the normal ranges of Schelonka et al . Results of neutrophil analyses were not used to determine duration of therapy . Fifty percent of asymptomatic neonates were seen postdischarge to ascertain recurrent infection . Local patient charges were examined . RESULTS: Ninety-six percent of neonates were asymptomatic and had negative cultures, and antibiotics were discontinued at 48 hours . A total of 2427 neutrophil counts were analyzed . Although abnormal neutrophil values were more frequent in infected or symptomatic neonates, 99% of asymptomatic neonates had > or = 1 abnormal value . The specificity and negative predictive values for abnormal neutrophil values ranged between 0.12 and 0.95 and 0.91 and 0.97, respectively; sensitivity was 0.27 to 0.76 . Significant differences in interpretation of the initial neutrophil values were noted, depending on the normal values used . Follow-up was performed for 373 asymptomatic neonates until 3 weeks' postnatal age . Eight required rehospitalization; none had evidence of bacterial infection . If neutrophil values had been used to determine duration of antibiotics, then local costs would have increased by 76,000 dollars to 425,000 dollars per year . CONCLUSIONS: Single or serial neutrophil values do not assist in the diagnosis of early-onset infection or determination of duration of antibiotic therapy in asymptomatic, culture-negative neonates who are > or = 35 weeks' gestation and are delivered of women with suspected chorioamnionitis.

Ophthalmology, 2004 May, 111(5), 1023 - 8
Orbital myositis associated with Borrelia burgdorferi (Lyme disease) infection; Carvounis PE et al.; OBJECTIVE: To report on the clinical findings in a patient with isolated left inferior rectus myositis associated with serologically confirmed Borrelia burgdorferi infection . DESIGN: Interventional case report . TESTING: Comprehensive clinical, laboratory, and imaging evaluation . RESULTS: Contrast-enhanced computed tomography showed a swollen inferior rectus muscle with infraorbital soft tissue swelling in a patient with diplopia and prior symptoms consistent with manifestations of Lyme disease . Positive serum and cerebrospinal fluid antibodies to B . burgdorferi by enzyme-linked immunoassay were confirmed by Western blot, and the cerebrospinal fluid/serum antibody ratio was elevated . No alternative cause for orbital myositis was found, and treatment with antibiotics resulted in a complete recovery . CONCLUSIONS: Orbital myositis should be added to the expanding list of ophthalmic manifestations of Lyme disease . Correct diagnosis and appropriate antibiotic therapy may reduce the likelihood of further neurologic or ophthalmologic sequelae.

Scand J Infect Dis, 2004, 36(3), 192 - 7
The use of CRP tests in patients with respiratory tract infections in primary care in Sweden can be questioned; Andre M et al.; A diagnosis-antibiotic prescribing study was performed in 5 counties in Sweden during 1 week in November in 2000 and 2002 respectively . As a part of the study, the use and results of C-reactive protein (CRP) tests in relation to duration of symptoms and antibiotic prescribing in 6778 patients assigned a diagnosis of respiratory tract infections were analysed . In almost half (42%) of the patients, a CRP test was performed . The majority of CRP tests (69%) were performed in patients assigned diagnosis upper respiratory tract infection, where the test is not recommended . Overall, there was a minor decrease in antibiotic prescribing when CRP was used (41%), in comparison to 44% of the patients where no CRP was performed (p < 0.01) . Patients assigned diagnoses implying a bacterial aetiology were prescribed antibiotics irrespective of result of CRP or length of symptoms before consultation . For patients assigned viral diagnoses, antibiotic prescribing increased with increasing duration of symptoms and increasing value of CRP . The use of CRP decreased antibiotic prescribing in patients assigned to viral diagnoses and with longstanding symptoms (p < 0.001) . However, 59% of the patients assigned viral diagnoses with CRP > or = 25 received antibiotics, which seems to indicate a misinterpretation of CRP and a non-optimal use of antibiotics.

Acta Neurochir (Wien), 2004 May, 146(5), 463 - 7 Epub 2004 Mar 22.
Infected CNS infusion pumps . Is there a chance for treatment without removal?
Boviatsis EJ, Kouyialis AT, Boutsikakis I, Korfias S, Sakas DE.
BACKGROUND: Intrathecal baclofen administration by means of an implantable pump is nowadays a safe and effective method in the treatment of spasticity . One of the rare but devastating complications of this technique is pump infection, with a variety of Gram (-) and Gram (+) organisms being involved . Treatment of these infections, according to international literature, requires removal of the device and appropriate antibiotic therapy . METHOD: This article reports the authors experience in treating 3 patients with severe, medically intractable spasticity, suffering from infection of the intrathecally-delivering pump . A decision was made not to replace the device, but to treat this complication with pump disinfection and with a new treatment modality that has never been used before, the intra-pocket administration of antibiotics . FINDINGS: In all cases the infection was eradicated and the integrity of the pump maintained . None of the patients required a procedure under general anesthesia . CONCLUSIONS: Removal should no longer be considered the first treatment option in infections of intrathecally delivering pumps, especially those due to non-adherent bacteria, with mild clinical symptomatology . An initial attempt should always be made for conservative treatment . Intra-pocket administration of antibiotics helps in achieving high drugs levels locally, and may prove an important element in our armamentarium against such infections .

J Mol Model (Online), 2004 Jun, 10(3), 223 - 32 Epub 2004 Apr 30.
Molecular aspects of the interaction between amphotericin B and a phospholipid bilayer: molecular dynamics studies; Sternal K et al.; Amphotericin B (AmB) is a polyene macrolide antibiotic used to treat systemic fungal infections . The molecular mechanism of AmB action is still only partly characterized . AmB interacts with cell-membrane components and forms membrane channels that eventually lead to cell death . The interaction between AmB and the membrane surface can be regarded as the first (presumably crucial) step on the way to channel formation . In this study molecular dynamics simulations were performed for an AmB-lipid bilayer model in order to characterize the molecular aspects of AmB-membrane interactions . The system studied contained a box of 200 dimyristoylphosphatidylcholine (DMPC) molecules, a single AmB molecule placed on the surface of the lipid bilayer and 8,065 water molecules . Two molecular dynamics simulations (NVT ensemble), each lasting 1 ns, were performed for the model studied . Two different programs, CHARMM and NAMD2, were used in order to test simulation conditions . The analysis of MD trajectories brought interesting information concerning interactions between polar groups of AmB and both DMPC and water molecules . Our studies show that AmB preferentially took a vertical position, perpendicular to the membrane surface, with no propensity to enter the membrane . Our finding may suggest that a single AmB molecule entering the membrane is very unlikely.FIGURE The figure presents the whole structure of the system simulated-starting point . AmB is presented as a space-filling model, DMPC molecules- green sticks, water molecules- red sticks

Nippon Ishinkin Gakkai Zasshi, 2004, 45(2), 77 - 81
{Drug discovery in the new era: exploratory research on novel antifungal agents}; Yagisawa M; The major antifungal agents currently used in clinics fall into classes of either antibiotics or azoles . Recent introduction of a candin-antibiotic, micafungin, into clinical practice is expected to greatly improve the outcome of therapy in deep mycoses . However, there still exist many mycoses which are hard to treat even with application of a variety of antifungal agents . With this situation of chemotherapy in mycoses, development of novel antifungal agents with good profiles in efficacy and safety and superior to those currently available are anticipated to be discovered by exploratory research . The major target worldwide in the research and development of novel antifungal agents is azole-class compounds . However, among the antifungal antibiotics now being developed, several compounds are being subjected to clinical evaluation based on their novel mechanisms of action and on their non-susceptible feature of cross-resistance to existing antifungal agents.

Curr Opin Ophthalmol, 2004 Jun, 15(3), 232 - 7
Advances in knowledge and treatment: an update on endophthalmitis; Busbee BG; PURPOSE OF REVIEW: In an area of increased willingness to perform surgery as surgical techniques are refined, comes the unavoidable complication of endophthalmitis . Because complete elimination of postsurgical endophthalmitis appears unattainable, strategies directed at optimal prevention, diagnosis, and management are constantly pursued . RECENT FINDINGS: Recent reports of the various aspects of endophthalmitis were analyzed from the leading peer-reviewed ophthalmic journals . SUMMARY: The author reviews the recent work concerning the factors that affect visual prognosis in postsurgical endophthalmitis.

Jpn J Infect Dis, 2004 Apr, 57(2), 33 - 6
Investigation of atypical bacteria and virus antigens in respiratory tract infections by use of an immunofluorescence method; Kaygusuz S et al.; In this study an immunofluorescence (IF) method was used to investigate the antigens of viruses and atypical bacteria in respiratory tract infections (RTI) in pediatric and adult age groups . In this prospective study of 2 years (1998-2000), IF was used to investigate the antigens of 7 viral and 3 atypical bacteria to be used for the etiological diagnosis of RTI . Sputum (33.6%) and nasopharyngeal aspirate specimens were obtained from pediatric patients (Group I, 76 cases) and adults (Group II, 135 cases) with RTI symptoms . Antigen detection rates were found to be 44.7% in Group I and 67.4% in Group II (P < 0.05) . The following rates for specific antigens in Groups I and II, respectively, were as follows: Chlamydia pneumoniae, 17.1 and 13.3% (P > 0.05); Mycoplasma pneumoniae, 0 and 9.6% (P < 0.05); influenza A virus, 3.9 and 16.3% (P < 0.05); adenovirus, 3.9 and 14.8% (P < 0.05); parainfluenza virus type 1, 5.3 and 7.4% (P > 0.05); respiratory syncytial virus, 9.2 and 1.5% (P < 0.05); parainfluenza virus type 2, 3.9 and 3%(P > 0.05); and influenza B virus, 1.3 and 1.5% (P > 0.05) . Mixed agents were found at a rate of 2.6 and 3.7% (P > 0.05) in Groups I and II, respectively . Parainfluenza virus type 3 and Legionella pneumophila antigens were not found . Since detecting etiological agents provides an important guide for determining the most appropriate antibiotic therapy, this IF method could be applied in clinical practice for arriving at a correct diagnosis and administration of effective treatment.

J Antimicrob Chemother, 2004 Jun, 53(6), 1101 - 4 Epub 2004 Apr 29.
Treatment of acute Chlamydia pneumoniae infection with telithromycin in C57BL/6J mice; Tormakangas L et al.; OBJECTIVES: The efficacy of telithromycin, a new ketolide antibiotic, was investigated in the treatment of acute Chlamydia pneumoniae infection in a mouse model . METHODS: C57BL/6J mice were inoculated intranasally, and the effects of three different doses of telithromycin (25, 50 and 100 mg/kg) were assessed after 5 and 10 days of treatment . Lungs for culture, PCR, histopathology, and blood for serum samples were collected immediately after each treatment period and at 3 weeks post-inoculation . C . pneumoniae-specific antibodies were analysed, and the effect of treatment was assessed by culture, detection of C . pneumoniae DNA and determination of histopathological inflammatory changes in mouse lungs . RESULTS: Culture negativity in the lungs was achieved with the higher doses, 50 and 100 mg/kg, after 10 days of treatment . C . pneumoniae DNA was not totally eradicated with the treatments, but the groups treated with 50 and 100 mg/kg doses for 10 days had the lowest DNA positivity rates (10%) 3 weeks after the inoculation . In lung histopathology, the efficacy of telithromycin on inflammatory changes was also dose-dependent: higher doses were more effective in reducing the inflammatory reaction . Overall, the 25 mg/kg dose had a weaker effect compared with the others . CONCLUSIONS: Telithromycin had both time- and dose-dependent effects on the eradication of chlamydia and on reducing infection-induced inflammatory changes in mouse lungs.

Gastroenterol Hepatol, 2004 May, 27(5), 317 - 9
{Liver abscess and Crohn' disease . Report of 3 cases}; Molina Infante J et al.; Liver abscess is a rare complication of Crohn's disease . Its prevalence and mortality are higher in patients with Crohn's disease than in the general population . Owing to its nonspecific clinical presentation, which may be mistaken for reactivation of Crohn's disease or be masked by simultaneous steroid therapy, a high index of suspicion is required for an early diagnosis and prompt treatment . We report 3 cases of Crohn's disease complicated with liver abscess in which the only common features were the absence of clinical or even endoscopic activity of Crohn's disease at diagnosis and the presence of an anastomotic leak due to right ileocolectomy in the previous year . In all patients, outcome was satisfactory with antibiotic therapy and percutaneous catheter drainage.

Hypertens Pregnancy, 2004, 23(1), 121 - 7
Septic pelvic thrombophlebitis and preeclampsia are related disorders; Isler CM et al.; OBJECTIVE: To elicit factors associated with the postpartum development of septic pelvic thrombophlebitis in a single large referral tertiary patient population . METHODS: A nine-year single institution retrospective case review of all patients with enigmatic fever and septic pelvic thrombophlebitis was analyzed . RESULTS: A total of 55 patients with septic pelvic thrombophlebitis were provided care during the study interval . The average gestational age at delivery was 36.8 +/- 4.3 weeks . The most prevalent concurrent medical complication of pregnancy was preeclampsia (45%) while chorioamnionitis affected only 13% . The average length of ruptured membranes was 22.8 +/- 56.8 hours (median 10.5, 95% confidence interval {CI} 7.0-38.7 hours), with 22% of patients undergoing amnion rupture at the time of cesarean delivery . Prolonged (>24 hours) amnion rupture occurred in only 9% of patients . Most affected patients were delivered abdominally (91%) but a minority delivered vaginally (9%) . Antibiotic therapy for presumed infection was initiated at 27.4 +/- 24.6 hours postpartum . Subsequently intravenous heparin therapy was initiated 128.9 +/- 54.2 hours thereafter enigmatic fever defervesed 37.2 +/- 36.8 hours later (median 34.0, 95% CI 27.2-47.3 hours) . Patients received 6.3 +/- 1.8 days of heparin therapy . CONCLUSION: In this series, septic pelvic thrombophlebitis was frequently preceded by cesarean delivery and commonly associated with preeclampsia . Unexpectedly, a small number of patients suffered prolonged rupture of membranes or chorioamnionitis . We speculate that the cesarean delivery of a population of at-risk patients with preeclampsia may predispose them to develop septic pelvic thrombophlebitis.

Ann Clin Biochem, 2004 May, 41(Pt 3), 245 - 7
Limitations of 17-hydroxyprogesterone in investigating neonatal hyponatraemia; Ismail AA et al.; Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a possible cause of hyponatraemia in the neonate . Elevated 17-hydroxyprogesterone (17-OHP) is considered diagnostic of the condition, although there have been reports of anomalous high concentrations, up to 110 nmol/L, in premature, sick infants subsequently shown to have normal adrenocortical function . We describe a case of a 6-week-old girl with a chest infection and hyponatraemia whose plasma 17-OHP concentration was 300 nmol/L, well within the range associated with 21-hydroxylase deficiency . However, there was no genital ambiguity and plasma cortisol was also significantly elevated, raising the possibility of generalized adrenal hyperstimulation rather than CAH . The patient was treated with antibiotic and saline infusions but no steroids . CAH was subsequently excluded by normal 17-OHP and cortisol responses to Synacthen stimulation . In sickness, an increased plasma 17-OHP concentration may not be synonymous with 21-hydroxylase deficiency, even when grossly raised . Simultaneous measurement of plasma cortisol could aid interpretation and avoid potential misdiagnosis, especially in male infants.

Am Fam Physician, 2004 Apr 15, 69(8), 1949 - 56
Hand and wrist injuries: Part II . Emergent evaluation; Daniels JM 2nd et al.; Primary care physicians must be able to recognize wrist and hand injuries that require immediate attention . A complete history and physical examination, including assessment of distal limb function, are essential . Hemorrhage control is necessary in patients with vessel lacerations and amputations . Amputations require an understanding of the indications and contraindications in the management of the amputated limb . High-pressure injection injuries and compartment syndromes require a high index of suspicion for early recognition . Infectious entities include "fight bite," open fractures, purulent tenosynovitis, animal bites, and retained foreign bodies . Tendon disruptions should be recognized early to optimize management.

Jpn J Antibiot, 2004 Feb, 57(1), 124 - 33
Concentration of clarithromycin and 14-R-hydroxy-clarithromycin in plasma of patients with Mycobacterium avium complex infection, before and after the addition of rifampicin; Yamamoto F et al.; Clarithromycin (CAM) and rifampicin (RFP) have both been recognized to be effective antibiotic agents against Mycobacterium avium complex (MAC) infection . Rifamycin derivatives including RFP and rifabutin modulate the CAM metabolism by inducing the hepatic cytochrome p-450 3A4 . To clarify the effect of RFP on the CAM metabolism, we measured the plasma concentration of CAM and 14-R-hydroxyclarithromycin (M-5), the major metabolite of CAM, in 9 patients suffering from MAC infection before and after the addition of RFP . After the addition of RFP, the mean plasma concentration of CAM significantly decreased, while that of M-5 did not . In addition, the amount of CAM + M-5 concentration also significantly decreased . As M-5 is less effective against MAC infection than CAM, more attention should thus be paid to the plasma CAM concentration in patients administered CAM and RFP concomitantly.

Kardiol Pol, 2004 Feb, 60(2), 142 - 4
{Infective endocarditis caused by Erysipelothrix rhusiopathiae--case report}; Grabowski M et al.; Infective endocarditis (IE) is an infectious disease, which leads to death when is untreated . In most cases IE is caused by typical bacteria . IE caused by atypical bacteria is rare . In this paper, we describe a female patient with IE caused by Erysipelothrix rhusiopathiae (ER) . Due to inflammation and leaflets' damage she underwent double-valve implantation (aortic and mitral ones) . A long-term antibiotic therapy was given with good outcome . We also describe the organism, types of human diseases caused by ER and treatment options.

J Perinatol, 2004 Jun, 24(6), 382 - 8
Nosocomial infection in the NICU: a medical complication or unavoidable problem?
Clark R, Powers R, White R, Bloom B, Sanchez P, Benjamin DK Jr.
Nosocomial sepsis is a serious problem for neonates who are admitted for intensive care . As it is associated with increases in mortality, morbidity, and prolonged length of hospital stay, both the human and fiscal costs of these infections are high . Although the rate of nosocomial sepsis increases with the degree of both prematurity and low birth weight, no specific lab test has been shown to be very useful in improving our ability to predict who has a "real" blood-stream infection and, therefore, who needs to be treated with a full course of antibiotics . As a result, antibiotic use is double the rate of "proven" sepsis and we are facilitating the growth of resistant organisms in the neonatal intensive care unit . The purpose of this article is to review the topic of nosocomial infections in neonates.

J Clin Gastroenterol, 2004 May-Jun, 38(5 Suppl), S2 - 7
The natural history of diverticulitis: fact and theory; Floch MH et al.; Epidemiological and anatomic evidence indicates that approximately 60% of humans of westernized societies living into the sixth decade will develop diverticulosis of the colon . The cause remains unknown, but epidemiological studies indicate it is a combination of decreased dietary fiber intake and increased intracolonic pressure . The intraluminal pressure exerted on the wall causes a diverticular outpocketing at any one of the three areas in which vessels enter the wall . In this paper, we advance a hypothesis that fiber deficiency not only leads to diverticula formation but also causes a change in the microecology that results in decreased colon immune response and permits a low-grade chronic inflammatory process that precedes a full-blown acute diverticulitis . Pathophysiologic studies reveal that complications do not occur until there is microperforation through the wall of the diverticulum into the pericolic tissue . The perforation might be small and cause a microabscess, or extend to a phlegmon, or extend to a large abscess formation . Free perforation occurs rarely, but fistulization does occur and most commonly to the bladder . The clinical findings vary . Most often, the clinical picture is one of fever, abdominal pain, a change in bowel habit, and localizing findings associated with leukocytosis . Computerized tomography scanning has become the procedure of choice to evaluate the symptoms since it is of less risk than a barium enema and obtains more information . The differential diagnosis may be difficult but usually can be made with accuracy . Medical treatment is preferred with appropriate antibiotic therapy and variations in fiber intake . When abscess occurs, percutaneous drainage may be tried, but when it is unsuccessful, surgical intervention is necessary . Sudden hemorrhage from a vessel in diverticula may also occur . It is estimated that approximately 20% of all patients that develop diverticula will have either inflammatory or bleeding episodes . In conclusion, fiber deficiency results in diverticular formation and a chronic inflammation that may progress to acute or chronic diverticulitis that can be treated medically but may require surgical intervention.

Pediatr Crit Care Med, 2004 May, 5(3), 286 - 8
Polyarteritis nodosa with central nervous system involvement mimicking meningoencephalitis; Paula De Carvalho Panzeri Carlotti A et al.; OBJECTIVE: To describe a patient who had polyarteritis nodosa with central nervous system involvement mimicking infectious meningoencephalitis . DESIGN: Case report . SETTING: Pediatric intensive care unit of a university hospital . Patient: A 9-yr-old boy with prolonged fever, headache, decreased level of consciousness, neck stiffness, and papilledema . RESULTS: Cerebrospinal fluid examination showed pleocytosis and a high protein level . After neurologic deterioration resulted from the initial treatment with antibiotic, the combination of clinical and laboratory findings with neuroradiologic features led to suspected systemic vasculitis . The patient was treated subsequently with corticosteroid, which resulted in great improvement . Biopsy of a skin lesion confirmed the diagnosis of polyarteritis nodosa . CONCLUSIONS: Critical care physicians must recognize neurologic manifestation patterns of systemic vasculitides because appropriate diagnosis and therapy result in significantly improved morbidity and mortality.

Anesthesiology, 2004 May, 100(5), 1088 - 100
Altered cell-mediated immunity and increased postoperative infection rate in long-term alcoholic patients; Spies CD et al.; BACKGROUND: Preoperative alteration of T cell-mediated immunity as well as an altered immune response to surgical stress were found in long-term alcoholic patients . The aim of this study was to evaluate perioperative T cell-mediated immune parameters as well as cytokine release from whole blood cells after lipopolysaccharide stimulation and its association with postoperative infections . METHODS: Fifty-four patients undergoing elective surgery of the aerodigestive tract were included in this prospective observational study . Long-term alcoholic patients (n = 31) were defined as having a daily ethanol consumption of at least 60 g and fulfilling the Diagnostic and Statistical Manual of Mental Disorders for either alcohol abuse or alcohol dependence . The nonalcoholic patients (n = 23) were defined as drinking less than 60 g ethanol/day . Blood samples to analyze the immune status were obtained on morning before surgery and on the morning of days 1, 3, and 5 after surgery . RESULTS: Basic patient characteristics did not differ between groups . Before surgery, the T helper 1:T helper 2 ratio (Th1: Th2) was significantly lower (P < 0.01), whereas plasma interleukin 1beta and lipopolysaccharide-stimulated interleukin 1ra from whole blood cells were increased in long-term alcoholic patients . After surgery, a significant suppression of the cytotoxic lymphocyte ratio (Tc1:Tc2), the interferon gamma:interleukin 10 ratio from lipopolysaccharide-stimulated whole blood cells, and a significant increase of plasma interleukin 10 was observed . Long-term alcoholics had more frequent postoperative infections compared with nonalcoholic patients (54%vs . 26%; P = 0.03) . CONCLUSIONS: T helper cell-mediated immunity was significantly suppressed before surgery and possibly led to inadequate cytotoxic lymphocyte and whole blood cell response in long-term alcoholic patients after surgery . This altered cell-mediated immunity might have accounted for the increased infection rate in long-term alcoholic patients after surgery.

Plast Reconstr Surg, 2004 May, 113(6), 1634 - 44
The infected or exposed breast implant: management and treatment strategies; Spear SL et al.; Among the potential complications associated with the use of breast implants are the risks of periprosthetic infection and device extrusion . There is little published information about the effective management of these situations . Conservative recommendations include antibiotic therapy and removal of the implant until resolution of the infection or until the wound has healed . A retrospective review identified patients with periprosthetic infection or threatened or actual device exposure treated by the senior author . Twenty-four patients encompassing 26 affected prostheses were available for review and were classified into seven groups based on initial presentation as follows: group 1, mild infection (n = 8); group 2, severe infection (n = 4); group 3, threatened exposure without infection (n = 3); group 4, threatened exposure with mild infection (n = 3); group 5, threatened exposure with severe infection (n = 1); group 6, actual exposure without clinical infection (n = 5); and group 7, actual exposure with infection (n = 2) . To salvage the prosthesis in these patients, various treatment strategies were utilized . All patients with a suspected infection or device exposure were started immediately on appropriate antibiotic therapy (oral antibiotics for mild infections and parenteral antibiotics for severe infections) . Salvage methods included one or more of the following: antibiotic therapy, debridement, curettage, pulse lavage, capsulectomy, device exchange, primary closure, and/or flap coverage . Twenty (76.9 percent) of 26 threatened implants with infection or threatened or actual prosthesis exposure were salvaged after aggressive intervention . The presence of severe infection adversely affected the salvage rate in this series . A statistically significant difference exists among those patients without infection or with mild infection only (groups 1, 3, 4, and 6); successful salvage was achieved in 18 (94.7 percent) of 19 patients, whereas only two of seven of those implants with severe infection (groups 2, 5, and 7) were salvaged (p = 0.0017) . Ten (90.9 percent) of 11 devices with threatened or actual exposure, not complicated by severe infection (groups 3, 4, and 6), were salvaged . Several treatment strategies were developed for periprosthetic infection and for threatened or actual implant exposure . Patients with infection were placed on oral or intravenous antibiotics; those who responded completely required no further treatment . For persistent mild infection or threatened or actual exposure, operative intervention was required, including some or all of the following steps: implant removal, pocket curettage, partial or total capsulectomy, debridement, site change, placement of a new implant, and/or flap coverage; the menu of options varied with the precise circumstances . No immediate salvage was attempted in five cases, due to either severe infection, nonresponding infection with gross purulence, marginal tissues, or lack of options for healthy tissue coverage . Based on the authors' experience, salvage attempts for periprosthetic infection and prosthesis exposure may be successful, except in cases of overwhelming infection or deficient soft-tissue coverage . Although an attempt at implant salvage may be offered to a patient, device removal and delayed reinsertion will always remain a more conservative and predictable option.

Artif Organs, 2004 May, 28(5), 483 - 6
Clinical experience with molecular adsorbent recirculating system (MARS) in patients with drug-induced liver failure; Zhou XM et al.; The molecular adsorbent recirculating system (MARS) is a novel extracorporeal technique for liver support . We report the clinical results in a group of fourteen patients with drug-induced liver failure . Fourteen patients, aged 22-83 years, with acute or subacute liver failure {mean Child-Turcotte-Pugh (CTP) score 11 (range 8-15)} due to the intake of various drugs (diet pill overdose-2; Chinese traditional medicine (CTM)-4; antibiotic, paracetamol, tuberculostatic, or vasodilator abuse-8) were treated with one to seven sessions of MARS . Beneficial effects such as the improvement of encephalopathy and prothrombin activity, as well as a reduction of bilirubin and ammonia were recorded during MARS treatments . Thirteen out of fourteen patients survived the hospitalization (93%), and two of the discharged patients died during the follow-up of 6-12 months . The overall survival rate was about 79% . MARS therapy can contribute to the improved treatment of drug-induced liver failure patients.

J Am Chem Soc, 2004 May 5, 126(17), 5396 - 402
Filipin orientation revealed by linear dichroism . Implication for a model of action; Lopes SC et al.; The organization of the polyene antibiotic filipin in membranes containing cholesterol is a controversial matter of debate . Two contradictory models exist, one suggesting a parallel and the other perpendicular organization of filipin with respect to the plane of the membrane . UV-vis linear dichroism, ATR-FTIR, and fluorescence anisotropy decay techniques were combined to study the orientation of filipin in model systems of membranes composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or 1,2-palmitoyl-sn-glycero-3-phosphocholine (DPPC) with and without cholesterol . Filipin's orientation is determined by the presence/absence of cholesterol when it is inserted in gel crystalline phase model membranes . When cholesterol (33%) is present in DPPC bilayers, filipin stands perpendicular to the membrane surface as expected in "pore-forming" models . At variance, absence of cholesterol leaves filipin in an essentially random organization in the lipidic matrix . In liquid crystalline phase bilayers (POPC) filipin's orientation is perpendicular to the membrane surface even in absence of cholesterol . Thus filipin's activity/organization depends not only on cholesterol presence but also in the lipid phase domain it is inserted in . These findings were combined with spectroscopy and microscopy data in the literature, solving controversial matters of debate.

J Med Liban, 2002 Sep-Dec, 50(5-6), 216 - 25
Medication use, gender, and socio-economic status in Lebanon: analysis of a national survey; Makhlouf Obermeyer C et al.; From data collected in Lebanon by the 1999 National Household Health Expenditures and Utilization Survey an analysis was made of reported medication use (n = 14,142) . Seventy-two percent of the population aged 25-64 reported taking a medication in the month preceding the survey . Medications with high frequencies of reported use were analgesics, psychotropics, antibiotics and vitamins . Women were more than one and a half times more likely than men to report taking any medication (OR = 1.6), and significantly more likely to report taking eight of the 19 medication types analyzed . Analyses of the association of medication use with socio-economic variables show different effects for education and employment (inversely correlated with higher use), and higher socio-economic status (positively correlated with higher use) . Multivariate analyses were carried out on two of the frequently used medications, antibiotic and prescription psychotropic use, to further explore the simultaneous effects of socio-economic variables The results of the analysis high-light a number of potential areas which may be targeted for intervention, in particular the higher use of antibiotics in rural areas, the greater use of psychotropics by women, and the possible obstacles to obtaining needed medications for those with lower incomes.

J Nanosci Nanotechnol, 2004 Jan-Feb, 4(1-2), 1 - 22
Supported membrane nanodevices; Anrather D et al.; Supported membrane nanodevices are based on natural or artificial ion channels embedded in a lipid membrane deposited on a chip wafer . Membrane conductance is modulated by biorecognitive events, with the use of intrinsic binding sites of the ion channel or via artificial sites fused to the channel protein . Artificial ion gates are constructed by coupling a specific ligand for the analyte near the channel entrance or a site important to triggering channel conformation . The binding event leads to the closure of the ion channel or induces a conformational change of the channel, reducing the ion flux . The signal transduced from the device is the decrease in the ion flux-induced electron current at a silver-silver chloride electrode at ultimate single-molecule sensitivity . Among the natural ion channels, gramicidin A, a transport antibiotic, was found to be most suitable, and thus was used by AMBRI, Australia, to set up prototypes of membrane biochips, using self-association of the dimer . Covalent dimerization-based devices, developed by the Vienna group, make use of the down-regulation of the permanently open membrane-spanning bisgramicidine ion channel . The reactive group at the C-terminus, a hydroxy group, allows precise coupling of the analyte-binding moiety in gramicidin as well as bisgramicidin . The device is set up with bilayer membranes deposited on apertures of a hydrophobic frame structure produced via microlithography, facing an aqueous or hydro-gel micro-environment on both sides, constructing black lipid membranes or patch-clamp devices "on chip." The setup of the device needs gel membrane supports that allow membrane formation and contribute to the stability of the bilayer by exposure of functional groups that promote electrostatic interaction and formation of hydrogen bridges and enable the introduction of covalent spacers and anchors . Photo-cross-linked polyvinylpyrrolidone and polyacrylamide, electropolymerized polydiaminobenzene and coated agarose, as well as various chemical modifications of these polymers, were employed as membrane supports . With optimized assemblies, the membrane support did allow the formation of stable bilayer membranes, proved by "gigaseal" (electrical sealing with giga-ohm resistance) to be free of any point defects in the lipid assembly . Supports with and without hydrophilic and hydrophobic anchors were studied with reference to promoting the formation of a self-assembled membrane, to their electric resistance, and to the capability to insert functional ionophores . All components, including novel chemically engineered ion channels, novel amphiphilic lipids, a microlithographically designed chip, isolating polymer frames, and a hydrogel membrane support, are combined in the new bionanodevice . Sensitivity and specificity were proved, for example, with the use of an antibody-antigen couple down-regulating the ion flux through the membrane channel . Single ion channels incorporated in the supported lipid bilayer gave stable signals at an operational stability of several hours, which is already sufficient to test and screen for membrane receptors but still insufficient to use this device as a sensor for off-site application . Further optimization to increase operational and storage stability is done by a number of groups to allow a broad application of these devices.

No To Shinkei, 2004 Mar, 56(3), 231 - 5
{Garcin syndrome in a patient with rhinocerebral mucormycosis}; Mutsukura K et al.; Garcin syndrome is characterized by an unilateral cranial nerves involvement without sensory or motor long-tract disturbances . It is usually caused by tumor infiltrating in the skull base with osteolytic changes on radiological study . We report a case of 64-year-old man with history of alcohol overintake, who admitted local hospital, because of right periorbital edema and facial swelling . He noted right ptosis 2 weeks prior to admission . Neurological examination revealed right multiple cranial nerves involvement including II, III, IV, V, and VI cranial nerves . MR imaging of the brain showed marked paranasal sinusitis and abnormal infiltration of right orbital fat . Orbital apex syndrome related to paranasal sinusitis was diagnosed, and antibiotics was administered . But a few days after admission, he developed a right VII, IX, X cranial nerve palsy . He was transferred to our hospital because of acute development of left hemiparesis and deteriorated consciousness . MR imaging of the brain showed right internal carotid artery (ICA) occlusion, and infarction in right middle cerebral artery (MCA)'s territory . The diagnostic biopsy of the paranasal sinus showed mucorales hyphae, indicating that the pathological diagnosis was mucormycosis . Despite of antibiotic therapy included of amphotericin-B administration and strict control of diabetic mellitus, his sinusitis was gradually spread . His condition progressively deteriorated, and finally died of sepsis . Post-mortem examination revealed a widespread mucor infiltration in the dura mater without skull bone invasion . This case presented with unilateral multiple cranial nerve involvements (Garcin syndrome) followed by left hemiparesis associated with rhinocerebral mucormycosis . It is suggested that mucormycosis should be considered in case of Garcin syndrome without osteolysis in the skull base.

Arch Biochem Biophys, 2004 May 15, 425(2), 233 - 41
Genome analyses of Streptomyces peucetius ATCC 27952 for the identification and comparison of cytochrome P450 complement with other Streptomyces; Parajuli N et al.; We have determined the genome sequence of 8.7 Mb chromosome of Streptomyces peucetius ATCC 27952, which produces clinically important anthracycline chemotherapeutic agents of the polyketide class of antibiotics, daunorubicin and doxorubicin . The cytochrome P450 (CYP) superfamily is represented by 19 sequences in the S . peucetius . Among those, 15 code for functional genes, whereas the remaining four are pseudo genes . CYPs from S . peucetius are phylogenetically close to those of Streptomyces amermitilis . Four CYPs are associated with modular PKS of avermectin and two with doxorubicin biosynthetic gene cluster . CYP252A1 is the new family found in S . peucetius, which shares 38% identity to CYP51 from Streptomyces coelicolor A3 (2) . Nine CYPs from S . peucetius are found in the cluster containing various regulatory genes including rar operon, conserved in S . coelicolor A3 (2) and Streptomyces griseus . Although two ferredoxins and four ferredoxin reductases have been identified so far, only one ferredoxin reductase was found in the cluster of CYP147F1 in S . peucetius . To date, 174 CYPs have been described from 45 Streptomyces species in all searchable databases . However, only 18 CYPs are clustered with ferredoxin . The comparative study of cytochrome P450s, ferredoxins, and ferredoxin reductases should be useful for the future development and manipulation of antibiotic biosynthetic pathways.

FEBS Lett, 2004 Apr 30, 564(3), 333 - 9
Crystallographic analysis of AcrB; Pos KM et al.; A His-tagged derivative of the multidrug efflux pump AcrB could be crystallized in three different space groups (R3, R32 and P321) . Experimental MAD-phasing maps from R32 AcrB(His) crystals were obtained to a resolution of 3.5 A . Datasets of native and substrate soaked AcrB(His) crystals were collected at the Swiss Light Source X06SA beamline up to a resolution of 2.7 A and refinement of these data provided good quality electron density maps, which allowed us to complement the published AcrB structure (PDB code 1iwg) . Introduction of amino acids 860-865 and 868 lacking in the 1iwg structure and deletion of a highly disordered region (amino acids 669-678) improved R(free) and average B factors in the 2.7 A model . We could not identify significant densities indicating specific antibiotic binding sites in the AcrB R32 space group datasets under the soaking conditions tested.

Biophys Chem, 2004 Jun 1, 109(3), 333 - 44
Changes in drug 13C NMR chemical shifts as a tool for monitoring interactions with DNA; Boudreau EA et al.; The antibiotic drug, netropsin, was complexed with the DNA oligonucleotide duplex {d(GGTATACC)}2 to monitor drug 13C NMR chemical shifts changes . The binding mode of netropsin to the minor groove of DNA is well-known, and served as a good model for evaluating the relative sensitivity of 13C chemical shifts to hydrogen bonding . Large downfield shifts were observed for four resonances of carbons that neighbor sites which are known to form hydrogen bond interactions with the DNA minor groove . Many of the remaining resonances of netropsin exhibit shielding or relatively smaller deshielding changes . Based on the model system presented here, large deshielding NMR shift changes of a ligand upon macromolecule binding can likely be attributed to hydrogen bond formation at nearby sites .

Biochem Biophys Res Commun, 2004 May 21, 318(1), 119 - 24
Isolation and enrichment of skeletal muscle progenitor cells from mouse bone marrow; Bhagavati S et al.; There is great interest in the therapeutic potential of non-hematopoietic stem cells obtained from bone marrow called mesenchymal stem cells (MSCs) . Rare myogenic progenitor cells in MSC cultures have been shown to convert into skeletal muscle cells in vitro and also in vivo after transplantation of bone marrow into mice . To be clinically useful, however, isolation and expansion of myogenic progenitor cells is important to improve the efficacy of cell transplantation in generating normal skeletal muscle cells . We introduced into MSCs obtained from mouse bone marrow, a plasmid vector in which an antibiotic (Zeocin) resistance gene is driven by MyoD and Myf5 enhancer elements, which are selectively active in skeletal muscle progenitor cells . Myogenic precursor cells were then isolated by antibiotic selection, expanded in culture, and shown to differentiate appropriately into multinucleate myotubes in vitro . Our results show that using a genetic selection strategy, an enriched population of myogenic progenitor cells, which will be useful for cell transplantation therapies, can be isolated from MSCs.

Phytochemistry, 2004 Apr, 65(8), 1061 - 71
Hygrophorones A-G: fungicidal cyclopentenones from Hygrophorus species (Basidiomycetes); Lubken T et al.; Twenty new 5-(hydroxyalkyl)-2-cyclopentenone derivatives (hygrophorones) could be isolated from Hygrophorus latitabundus, H . olivaceoalbus, H . persoonii, and H . pustulatus . Their fungicidal activity was exemplarily tested . The hygrophorones have structural similarities to the antibiotic pentenomycin . Chemically, hygrophorones are 2-cyclopentenones with hydroxy or acetoxy substituents at C-4 and/or C-5 . An odd-numbered 1' oxidized alkyl chain (C(11), C(13), C(15), or C(17)) is attached at C-5 . In addition, from H . persoonii the new gamma-butyrolactone derivative {5-(E)-2-hydroxytetradexylidene-5H-furan-2-one} could be isolated . Some hygrophorones are responsible for the color reaction of the stipes of these fungi upon treatment with potassium hydroxide solution . Structural elucidations are based on 1D ((1)H, (13)C) and 2D (COSY, NOESY, HSQC, HMBC) NMR spectroscopic analyses as well as HR-FT-ICR-MS investigations.

Exp Eye Res, 2004 Jun, 78(6), 1077 - 84
Minocycline delays photoreceptor death in the rds mouse through a microglia-independent mechanism; Hughes EH et al.; PURPOSE: Minocycline, a semi-synthetic tetracycline antibiotic is reported to be neuroprotective in degenerative and ischaemic models of central nervous system disease, via mechanisms involving suppression of both cytotoxic microglial activity and caspase-dependent apoptosis . We have investigated the effect of minocycline treatment on a mouse model of retinitis pigmentosa, an inherited photoreceptor neurodegenerative disorder, and contrasted this with the effect of depleting retinal microglia using liposomal clodronate . METHODS: rds mice were treated intraperitoneally from the second postnatal day (P2) with either daily minocycline until P16, P18, P21, P24 and P27 or alternative day clodronate liposomes until P16 . Immunohistochemical and immunofluorescent methods were applied for the detection of microglia (F4/80) and apoptosis (TUNEL and caspase 3 activation) . RESULTS: Photoreceptor apoptosis was delayed by minocycline treatment but not, ultimately, prevented . Markedly reduced expression of activated caspase 3 was observed in photoreceptors at the early time point, corresponding with the reduced level of apoptosis . Delayed photoreceptor apoptosis due to minocycline treatment was associated with a 50% reduction in the numbers of microglia at early timepoints . Liposomal clodronate treatment also resulted in a marked reduction in the number of microglia (63% reduction in microglia), but in contrast to minocycline treatment, this had no effect on photoreceptor apoptosis . CONCLUSIONS: Minocycline appears to delay photoreceptor apoptosis through a microglia-independent action . Although microglial cytotoxicity has been implicated during other models of neurodegeneration, microglia are unlikely to play such a role in this model of photoreceptor dystrophy.

BMC Neurol . 2004 Apr 26;4(1):7.
Low dose intravenous minocycline is neuroprotective after middle cerebral artery occlusion-reperfusion in rats; Xu L et al.; BACKGROUND: Minocycline, a semi-synthetic tetracycline antibiotic, is an effective neuroprotective agent in animal models of cerebral ischemia when given in high doses intraperitoneally . The aim of this study was to determine if minocycline was effective at reducing infarct size in a Temporary Middle Cerebral Artery Occlusion model (TMCAO) when given at lower intravenous (IV) doses that correspond to human clinical exposure regimens . METHODS: Rats underwent 90 minutes of TMCAO . Minocycline or saline placebo was administered IV starting at 4, 5, or 6 hours post TMCAO . Infarct volume and neurofunctional tests were carried out at 24 hr after TMCAO using 2,3,5-triphenyltetrazolium chloride (TTC) brain staining and Neurological Score evaluation . Pharmacokinetic studies and hemodynamic monitoring were performed on minocycline-treated rats . RESULTS: Minocycline at doses of 3 mg/kg and 10 mg/kg IV was effective at reducing infarct size when administered at 4 hours post TMCAO . At doses of 3 mg/kg, minocycline reduced infarct size by 42% while 10 mg/kg reduced infarct size by 56% . Minocycline at a dose of 10 mg/kg significantly reduced infarct size at 5 hours by 40% and the 3 mg/kg dose significantly reduced infarct size by 34% . With a 6 hour time window there was a non-significant trend in infarct reduction . There was a significant difference in neurological scores favoring minocycline in both the 3 mg/kg and 10 mg/kg doses at 4 hours and at the 10 mg/kg dose at 5 hours . Minocycline did not significantly affect hemodynamic and physiological variables . A 3 mg/kg IV dose of minocycline resulted in serum levels similar to that achieved in humans after a standard 200 mg dose . CONCLUSIONS: The neuroprotective action of minocycline at clinically suitable dosing regimens and at a therapeutic time window of at least 4-5 hours merits consideration of phase I trials in humans in view of developing this drug for treatment of stroke.

Drug Dev Ind Pharm, 2004 Mar, 30(3), 289 - 96
In vitro skin permeation and retention of paromomycin from liposomes for topical treatment of the cutaneous leishmaniasis; Ferreira LS et al.; Paromomycin (PA), a very hydrophilic antibiotic, has been tested as an alternative topical treatment against cutaneous leishmaniasis (CL) . Although this treatment has shown promising results, it has not been successful in accelerating the recovery in most cases . This could be attributed to the low skin penetration of PA . Liposomal formulations usually provide sustained and enhanced drug levels in skin . The aim of this study was to prepare liposomal formulations containing PA and to investigate their potential as topical delivery systems of this antileishmanial . Large multilamellar vesicles (MLVs) were prepared by conventional solvent evaporation method . Large unilamellar vesicles (LUVs) were prepared by reverse-phase evaporation method . The lipids used were soybean phosphatidylcholine (PC) and PC:cholesterol (CH) (molar ratio 1:1) . The skin permeation experiments across stripped and normal hairless mice skin were performed in modified Franz diffusion cells . The PA entrapment in LUV liposomes (20.4 +/- 2.2%) was higher than that observed for MLV liposomes (7.5 +/- 0.9%) . Drug entrapment was 41.9 +/- 6.2% and 27.2 +/- 2.4% for PC and PC:CH LUV, respectively . The skin permeation was 1.55 +/- 0.31%, 1.29 +/- 0.40%, 0.20 +/- 0.08%, and 0.50 +/- 0.19% for PC LUV, PC:CH LUV, empty LUV +/- PA and aqueous solution, respectively . Controlled topical delivery, across stripped skin, was observed for PA entrapped in LUV liposomes.

Infect Control Hosp Epidemiol, 2004 Apr, 25(4), 319 - 24
Prevalence of nosocomial infections after surgery in Greek hospitals: results of two nationwide surveys; Gikas A et al.; OBJECTIVE: To determine the frequency and type of nosocomial infections (NIs) (especially surgical-site infections {SSIs}), risk factors, and the type and duration of antibiotic use among surgical patients in Greek hospitals . DESIGN: Two point-prevalence studies . SETTING: Fourteen Greek hospitals . PATIENTS: Those in the hospitals during two prevalence surveys undergoing surgery during their stay . RESULTS: In the 1999 survey, 129 of 1,037 surgical patients had developed 148 NIs (14.3%) . A total of 1,093 operations were registered, and 49 SSIs (4.5%) were found . In the 2000 survey, 82 of 868 surgical patients had developed 88 NIs (10.1%) . A total of 902 operations were registered, and 38 SSIs were detected (4.2%) . The median length of stay (LOS) for surgical patients without SSI was 10.0 days (range, 1-19 days); for patients who developed SSI it was 30 days (range, 1-52 days; P < .001) . The median LOS prior to surgery for patients without SSI was 1 day (range, 0-4 days); for patients who developed SSI it was 3 days (range, 0-7.5 days; P < .001) . Among 30 possible risk factors studied, wound class, LOS prior to surgery, and central venous catheterization were independent predictors of SSI . Median durations of prophylactic antibiotic therapy were 4 days (range, 1-14 days) and 6 days (range, 1-16 days) in the 1999 and 2000 surveys, respectively . CONCLUSION: Surgical patients in Greek hospitals suffered higher rates of SSI than did surgical patients in other developed countries while prophylactic antibiotics were used excessively.

Support Care Cancer, 2004 Jul, 12(7), 517 - 25 Epub 2004 Apr 24.
Topical polyene antifungals in hematopoietic cell transplant patients: tolerability and efficacy; Epstein JB et al.; PURPOSE: The effectiveness of amphotericin B oral suspension versus nystatin oral suspension for the prevention of oral colonization by Candida in hematopoietic cell transplant (HCT) patients was examined . METHODS: Prior to hematopoietic cell infusion, 40 patients receiving systemic fluconazole for prophylaxis were randomized to receive either amphotericin B oral suspension or nystatin oral suspension, q.i.d . The study continued to day 21 or until the patient was discharge from the hospital or withdrawn from the study . Oral examinations were conducted twice weekly, and adverse events and compliance were recorded . Cultures were taken for quantitative counts and species identification . Candida isolates were assessed for resistance to the oral antifungal agents . Blood was collected for assessment of amphotericin B levels . RESULTS AND DISCUSSION: Ulcerative mucositis occurred in 84.6% of patients undergoing HCT, and no correlation was observed between the severity of mucositis and the presence of oral Candida and the severity of mucositis . Systemic and topical antifungal treatment resulted in a decrease in the number of colonized patients (54.8% before treatment; 23.1% during treatment); however, oral colonization was not eliminated . Tolerability of the oral rinse products was limited, with greater noncompliance in the amphotericin B than the nystatin group . Reports of altered taste appeared to be greater in the amphotericin B group . Minimal absorption of amphotericin B was seen following oral rinsing (serum levels 0.12-0.50 microg/ml), and no consistent changes in organism susceptibility to polyenes were seen . The results suggest that topical antifungal rinses may further control oropharyngeal colonization by Candida in patients on systemic antifungals receiving HCT, but the effect is limited by tolerability and reformulation and should be considered in order to increase compliance.

Internist (Berl), 2004 Jun, 45(6), 669 - 76
{Rickettsioses of the spotted fever-group}; Bassetti S; Rickettsioses are among the most frequent causes of febrile diseases in travelers, as shown in several studies in the last years . Furthermore, since 1991, with the introduction of new testing methods, 8 new Rickettsia species (or new diseases) have been described . Typical symptoms of rickettsial infections are high fever, headaches and myalgias, frequently associated with a rash and/or an inoculation eschar ("tache noire") at the site of tick bite . The rapid recognition of a rickettsiosis and the immediate start of appropriate antibiotic therapy are important because some rickettsioses (e . g . the Rocky Mountain spotted fever) are associated with relevant morbidity and mortality . This paper reviews the spotted fever group rickettsioses.

Minerva Stomatol, 2004 Apr, 53(4), 179 - 83
Lithiasis of minor salivary glands of the upper lip . Clinico-pathological report of a case with unusual presentation; Favia G et al.; We report a rare case of lithiasis of the minor salivary glands (LMSG) of the upper lip, with a very atypical clinical presentation, firstly as a left hemifacial cellulitis and later, after antibiotic therapy, as a solid, firm and hard intramural nodule of the retrocommissural side of the upper lip; the needs of a wide spectrum of clinical differential diagnosis with calcified angiomas, salivary tumors, soft tissue tumors, phlogistic and neoplastic pathology of the local lymphnode, foreign body lesions, is underlined . The histological aspects of the lesion are described.

Rev Pneumol Clin, 2004 Feb, 60(1), 46 - 9
{Minocycline-induced neutrophilic alveolitis?}; Hammerer V et al.; A 53-year-old man was treated for hypoxic pneumonia . Alveolar lavage revealed neutrophilic alveolitis and search for an infectious agent was negative . Lung biopsy revealed discrete endo-alveolar edema and polymorphous infiltration in moderately thickened alveolar walls . After 17 days, an ineffective antibiotic regimen was replaced by corticosteroids . Clinical and radiological signs improved in a few days and pneumonia did not recur after corticosteroid withdrawal . The most likely causal agent was minocycline which the patient had received for two Years for the treatment of rhinophyma . Minocycline had been interrupted several weeks when the pulmonary disorder developed after re-introduction of minocycline . Different clinical manifestations of minocycline-induced lung disease have been described including eosinophilic pneumopathy, bronchiolitis obliterans with organized pneumonitis, and hypersensitivity pneumonitis . There has only been one report of polymorphonuclear neutrophils observed in the lavage fluid.

Nucleic Acids Res, 2004 Apr 23, 32(7), 2214 - 22 Print 2004.
Crystal structure of the {Mg2+-(chromomycin A3)2}-d(TTGGCCAA)2 complex reveals GGCC binding specificity of the drug dimer chelated by a metal ion; Hou MH et al.; The anticancer antibiotic chromomycin A3 (Chro) is a DNA minor groove binding drug belonging to the aureolic family . Chro likely exerts its activity by interfering with replication and transcription . Chro forms a dimer, mediated by a divalent metal ion, which binds to G/C-rich DNA . Herein we report the first crystal structure of Chro bound to d(TTG GCCAA)2 DNA duplex solved by multiwavelength anomalous diffraction (MAD) based on the chelated Co3+ ion . The structure of the Mg2+ complex was subsequently refined at 2.15 A resolution, which revealed two complexes of metal-coordinated dimers of Chro bound to the octamer DNA duplex in the asymmetric unit . The metal ion is octahedrally coordinated to the O1 and O9 oxygen atoms of the chromophore (CPH), and two water molecules act as the fifth and sixth ligands . The two coordinated water molecules are hydrogen bonded to O2 atoms of C5 and C13 bases . The Chro dimer binds at and significantly widens the minor groove of the GGCC sequence . The long axis of each chromophore lies along and stacks over the sugar-phosphate backbone with the two attached saccharide moieties (rings A/B and C/D/E) wrapping across the minor groove . DNA is kinked by 30 degrees and 36 degrees in the two complexes, respectively . Six G-specific hydrogen bonds between Chro and DNA provide the GGCC sequence specificity . Interestingly, DNA in concert with Chro appears to act as an effective template to catalyze the deamination of Co(NH3)6(3+), as shown by circular dichroism and crystal structure data . Our results present useful structural information for designing new anticancer drug derivatives in the future.

Sports Med, 2004, 34(5), 293 - 306
Potential interactions between exercise and drug therapy; Lenz TL et al.; Certain physiological changes caused by aerobic exercise can alter the pharmacokinetics of some drugs . A systematic review of the pharmacokinetic changes that can affect drugs as a result of aerobic exercise is provided . Eleven commonly used drugs are reviewed for their potential interaction with exercising patients . Serum concentrations of two beta-blocking agents, atenolol and propranolol, and one antibiotic, doxycycline, have shown to increase as a result of exercise . No pharmacokinetic changes have been found in exercising patients taking carvedilol or verapamil . Patients who exercise after taking digoxin experience a decreased digoxin serum concentration with an increased skeletal muscle concentration . The clearance of theophylline has been shown to decrease resulting in an increase in plasma half-life during exercise . The risk of hypoglycaemia may increase when patients with diabetes mellitus inject insulin into a muscle just prior to exercising that muscle . Increasing physical activity in patients taking warfarin has been shown to decrease the international normalised ratio . Much is still unknown regarding the interactions that exist between exercise and drug therapy . More studies need to be completed in this area before definite conclusions are made and clinical relevance can be established . Clinicians should be aware that the potential for such interactions exists, especially for drugs with a narrow therapeutic range and in patients who participate in extreme sporting activities.

Cochrane Database Syst Rev . 2004;(2):CD003964.
Interventions for preventing infection in nephrotic syndrome; Wu HM et al.; BACKGROUND: Infection is one of the most common complications and still remains a significant cause of morbidity and occasionally mortality in patients, especially children with nephrotic syndrome . Many different prophylactic interventions have been used or recommended for reducing the risks of infection in nephrotic syndrome in clinical practice . Whether the existing evidence is scientifically rigorous and which prophylactic intervention can be recommended for routine use based on the current evidence is still unknown . OBJECTIVES: To assess the benefits and harms of any prophylactic interventions for reducing the risk of infection in children and adults with nephrotic syndrome . SEARCH STRATEGY: We searched the Cochrane Renal Group Specialised Register (January 2003), The Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 1, 2003), MEDLINE and Pre-MEDLINE (1966 - February 2003), EMBASE (1980 - February 2003), China Biological Medicine Database (CBMdisc, 1979 - December 2002), reference lists of nephrology textbooks, review articles, relevant trials and abstracts from nephrology scientific meetings without language restriction . SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing any prophylactic interventions (pharmacological or non-pharmacological) for preventing any infection in children and adults with nephrotic syndrome . DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed and extracted information . Information was collected on method, participants, interventions and outcomes ( appearance of infection, mortality, quality of life and adverse events) . MAIN RESULTS: Five RCTs conducted in China, including 308 children with nephrotic syndrome were identified . No trials were identified in adults . All trials compared one kind of prophylactic pharmacotherapy (IVIG, thymosin or a compound of Chinese medicinal herbs - TIAOJINING) in addition to baseline treatment with baseline treatment alone . No RCTs were identified comparing antibiotic or non-pharmacological prophylaxis, or pneumococcal vaccination . Three trials showed a significantly better effect of IVIG on preventing nosocomial or unspecified infection in children with nephrotic syndrome (RR 0.39, 95% CI 0.18 to 0.82) . Thymosin and TIAOJINING were also effective for reducing the risks of infection in children with nephrotic syndrome with RR 0.50 (95%CI 0.26 to 0.97) and 0.59 (95%CI 0.43 to 0.81) respectively . No serious adverse events were reported . REVIEWERS' CONCLUSIONS: IVIG, thymosin and TIAOJINING may have positive effects on prevention of nosocomial or unspecified infection with no obvious serious adverse events in children with nephrotic syndrome . However the methodological quality of all trials was poor, the sample sizes small and all studies were from China, and thus there is no strong evidence on the effectiveness of these interventions.

Zentralbl Chir, 2004 Apr, 129(2), 136 - 8
{Improvement in surgical treatment of rectal cancer in the surgical department of County Hospital, Szekszard}; Zollei I et al.; 247 elective rectal operations were performed between 1st of Jan., 1996 till 31st of Dec., 2001 in our surgical department . The observation period was divided into one 4-year and one 2-year period . 148 operations were performed in the first and 99 in the second period . In the second period some personal, methodical and technical changes occurred . Age and sex distributions were similar, and the groups were comparable . The early postoperative mortality rate decreased from 9% to 4% . Due to the double stapling technique the rate of anterior rectal resections increased from 40% to 69% and the rate of abdomino-perineal rectal extirpation decreased from 43% to 23% in the same time . Large differences were found in the rate of palliative stoma performing operations, the rate decreased from 16% to 8% in the second period, so the quality of life of the patients improved . The operative time, the length of hospital stay and the rate of blood transfusions decreased as did the rate of postoperative infections . The new quality program improved the results significantly.

Antimicrob Agents Chemother, 2004 May, 48(5), 1892 - 4
Iron blocks the accumulation and activity of tetracyclines in bacteria; Avery AM et al.; The apparent sensitivities of several bacterial pathogens to tetracyclines varied by up to 128-fold with the medium content of Fe, but not of other metals . The effect of Fe was independent of superoxide dismutase activity and of intracellular Fe, but accumulation of tetracyclines was blocked in high-Fe medium . Thus, synergistic suppression of bacterial growth in the presence of a low Fe concentration and tetracyclines arises because of elevated antibiotic accumulation.

Clin Nurs Res, 2004 May, 13(2), 156 - 67
Factors affecting learning during health education sessions; McDonald DD et al.; Background noise and interruption were examined for their effects on learning health information . The final sample consisted of 48 college students randomly assigned to one of four conditions in a pretest-posttest, double-blind, 2 x 2 experiment comparing noise (noise/no noise) by interruption (interruption/no interruption) . Students viewed one of four videotapes about safe antibiotic use and then completed the posttest . The group watching the videotape with no distraction learned significantly more than the group watching the videotape with noise and with interruption . The results suggest that distraction during health teaching adversely affects the ability to learn health information.

Chir Narzadow Ruchu Ortop Pol, 2003, 68(5), 341 - 5
{Considerations in operative treatment of closed fractures}; Bielawski J; The principles that ought to be followed in closed fracture operative treatment have been presented . All relevant factors of surgical management were considered, beginning from qualification of the patient with motor system trauma for operative treatment, right choice of stabilization technique, as well as appropriate soft tissue and early posttraumatic care . It was emphasized that, even a "technically perfect" stabilization of fractured bone pieces using the right technique gave no guarantee of success if soft tissue care was inappropriate, inadequate was limb blood supply and if treatment of infection complicated cases in the early stage was solely limited to systematic antibiotic administration.

J Mass Spectrom, 2004 Apr, 39(4), 437 - 46
Application of liquid chromatography-ion trap mass spectrometry to the characterization of the 16-membered ring macrolide josamycin propionate; Govaerts C et al.; Coupled liquid chromatography and ion trap mass spectrometry (LC/MS) was used for the characterization of the semi-synthetic 16-membered ring macrolide josamycin propionate . On-line identification of impurities in this antibiotic complex was performed with an ion trap mass spectrometer without recourse to time-consuming isolation and purification procedures . Ion trap mass spectrometry is ideally suited to identification of impurities because it provides MSn capability, enabling multiple stages of mass spectrometry to obtain the maximum amount of structural information for a given molecule . The ion trap was used with an electrospray ionization source operated in the positive ion mode or with an atmospheric pressure chemical ionization source operated in the negative ion mode . The identity of the unknown compounds was deduced using the MS/MS and MSn collision-induced dissociation spectra of reference substances or structural analogs as interpretative templates, combined with knowledge about the nature of functional group fragmentation behavior . Given the importance attached to the identification of impurities of unknown identity in pharmaceutical substances, this study is useful for companies producing josamycin propionate . The knowledge of the fragmentation behavior is also of importance in further research on other 16-membered macrolides .

Nervenarzt, 2004 Oct, 75(10), 1016 - 21
{Fulminant meningoencephalitis associated with Mycoplasma pneumoniae infection in adults . Aggressive treatment enabled a good outcome}; Sparing R et al.; Mycoplasma pneumoniae (M . pn.) commonly causes respiratory tract infections in humans . In a certain percentage of cases it may also be associated with various peripheral and central nervous system manifestations . We report a case of a 38-year-old previously healthy man who presented with hemiplegia and somnolence after he had suffered from a febrile respiratory infection 10 days earlier . Clinical features and laboratory investigations supported the diagnosis of an acute M . pneumoniae-associated meningoencephalitis . He was treated by an aggressive antibiotic and immunomodulatory regimen over the course of several weeks in the neurocritical care unit . Decompressive hemicraniectomy was performed due to life-threatening raised intracranial pressure . However, the patient recovered almost completely and presented with a mild neurological deficit after 3 months . Based on this case we give a review of the literature and discuss potential pathomechanisms and diagnostic approaches.

Expert Opin Pharmacother, 2004 Apr, 5(4), 865 - 74
Antifungal therapy for keratomycoses; Ganegoda N et al.; Keratomycoses have recently emerged as an important cause of ocular morbidity, especially in third-world countries . Available antifungal agents are limited in their efficacy, due to limited penetration into the cornea, the fungistatic nature and the development of drug resistance . Effective usage of the available drugs is hampered by the inefficiency of currently available antibiotic sensitivity tests for fungal organisms . There is also limited knowledge regarding the ideal combination(s) of antifungal agents, including issues of synergism and antagonism . Despite these problems, recent publications indicate encouraging outcomes in the treatment of a large series of fungal keratitis . Advances include better drug formulations, new agents and novel methods of drug delivery into the eye . As our ability to deal with advanced fungal keratitis remains limited, the importance of early diagnosis has been stressed and molecular biological techniques may play an important role in the future . This article summarises the important new advances in these areas in the past 2 years and provides guidelines for the management of these serious corneal infections.

Org Lett, 2004 Apr 29, 6(9), 1477 - 80
Construction of a C(30-38) dioxabicyclo{3.2.1}octane subtarget for (+)-sorangicin A, exploiting a regio- and stereocontrolled acid-catalyzed epoxide ring opening; Smith AB 3rd et al.; {reaction: see text} In this paper, we report assembly of the novel dioxabicyclo{3.2.1}octane subtarget (-)-2, comprising the signature structural element of the potent antibiotic (+)-sorangicin A (1) . The synthesis was achieved in 15 steps (1.5% overall yield) via a series of acid-catalyzed epoxide ring openings . The first, facilitated by the complex of alkyne (+)-3 with Co(2)(CO)(8), proceeded in a highly regio- and stereoselective fashion.

J Natl Cancer Inst, 2004 Apr 21, 96(8), 586 - 94
Evidence for an association between Chlamydia psittaci and ocular adnexal lymphomas; Ferreri AJ et al.; BACKGROUND: Ocular adnexal lymphomas may be antigen-driven disorders; however, the source of the putative antigen or antigens is still unknown . Hence, we assessed whether Chlamydiae infection is associated with the development of ocular adnexal lymphomas . METHODS: The presence of Chlamydia psittaci, trachomatis, and pneumoniae DNA was investigated by polymerase chain reaction in 40 ocular adnexal lymphoma samples, 20 nonneoplastic orbital biopsies, 26 reactive lymphadenopathy samples, and peripheral blood mononuclear cells (PBMCs) from 21 lymphoma patients and 38 healthy individuals . Seven patients with chlamydia-positive PBMCs were treated with the antibiotic doxycycline, and objective response was assessed in four patients with measurable lymphoma lesions . Differences in Chlamydiae DNA detection between the case patients and the control subjects were analyzed using the Fisher exact test . All statistical tests were two-sided . RESULTS: Thirty-two of the 40 (80%) ocular adnexal lymphoma samples carried C . psittaci DNA, whereas all lymphoma samples were negative for C . trachomatis and C . pneumoniae . In contrast, none of the 20 nonneoplastic orbital biopsies (0% versus 80%; P<.001) and only three of 26 (12%) reactive lymphadenopathy samples (12% versus 80%; P<.001) carried the C . psittaci DNA . Nine of 21 (43%) patients with chlamydia-positive lymphomas carried C . psittaci DNA in their PBMCs, whereas none (0%) of the healthy PBMC donors carried C . psittaci DNA in their PBMCs (43% versus 0%; P<.001) . One month after doxycycline treatment, chlamydial DNA was no longer detectable in the PBMCs of all seven treated patients, and objective response was observed in two of the four evaluable patients . CONCLUSION: Patients with ocular adnexal lymphoma had a high prevalence of C . psittaci infection in both tumor tissue and PBMCs . Persistent C . psittaci infection may contribute to the development of these lymphomas, as was also supported by the clinical responses observed in this study with C . psittaci-eradicating antibiotic therapy.

Int Immunopharmacol, 2004 Apr, 4(4), 521 - 6
RNA degradation precedes DNA cleavage in autoreactive CD4 T cells suppressed by calicheamicin gamma1; Thomas S et al.; Calicheamicin gamma1 (Cal gamma1) is a hydrophobic enediyne antibiotic known to cleave the DNA and lead to apoptosis in a variety of cells . Herein, we show that Cal gamma1 exhibits a 1000-times stronger suppressogenic effect on antigen-specific (diabetogenic), and naive CD4 T cells than Doxorubicin (Dox), another strong apoptotic drug . The thymic precursors and mature T cells incubated with Cal gamma1 for only 30 min showed a drastic decrease or loss of cytokine production and proliferation following stimulation with the immunogenic peptide, or with CD3 and CD28 antibodies . The suppressogenicity of Cal gamma1 correlated with a rapid and non-selective degradation of RNA, whereas the DNA cleavage occurred at a later time point and at higher doses . Cal gamma1 may represent a potential therapeutic agent to eliminate self-reactive T cells in autoimmune diseases, providing that is delivered by antigen-specific T-cell ligands . Targeting of highly suppressogenic drugs such as Cal gamma1 to autoreactive T cells may reduce considerable the therapeutic dose and the drug-related side effects .

Vet Res, 2004 Mar-Apr, 35(2), 213 - 24
Tilmicosin-induced bovine neutrophil apoptosis is cell-specific and downregulates spontaneous LTB4 synthesis without increasing Fas expression; Lee WD et al.; The pathology of bacterial pneumonia, such as seen in the bovine lung infected with Mannheimia haemolytica, is due to pathogen virulence factors and to inflammation initiated by the host . Tilmicosin is a macrolide effective in treating bacterial pneumonia and recent findings suggest that this antibiotic may provide anti-inflammatory benefits by inducing polymorphonuclear neutrophilic leukocyte (PMN) apoptosis . Using an in vitro bovine system, we examined the cell-specificity of tilmicosin, characterized the changes in spontaneous leukotriene B4 (LTB4) synthesis by PMN exposed to the macrolide, and assessed its effects on PMN Fas expression . Previous findings demonstrated that tilmicosin is able to induce PMN apoptosis . These results were confirmed in this study by the Annexin-V staining of externalized phosphatidylserine and the analysis with flow cytometry . The cell-specificity of tilmicosin was assessed by quantification of apoptosis in bovine PMN, mononuclear leukocytes, monocyte-derived macrophages, endothelial cells, epithelial cells, and fibroblasts cultured with the macrolide . The effect of tilmicosin on spontaneous LTB4 production by PMN was evaluated via an enzyme-linked immunosorbent assay . Finally, the mechanisms of tilmicosin-induced PMN apoptosis were examined by assessing the effects of tilmicosin on surface Fas expression on PMN . Tilmicosin-induced apoptosis was found to be at least partially cell-specific, as PMN were the only cell type tested to die via apoptosis in response to incubation with tilmicosin . PMN incubated with tilmicosin under conditions that induce apoptosis spontaneously produced less LTB4, but did not exhibit altered Fas expression . In conclusion, tilmicosin-induced apoptosis is specific to PMN, inhibits spontaneous LTB4 production, and occurs through a pathway independent of Fas upregulation.

Neurosurg Focus . 1997 Jul 15;3(1):e3.
Microsurgical carpal tunnel release; Shapiro S; The author reports on a series of 482 patients who underwent primary carpal tunnel release (CTR) surgery beginning in 1987 . Two hundred twenty-five patients underwent CTR in the right hand, 169 patients underwent CTR in the left hand, and 88 patients underwent bilateral CTR surgery, for a total of 570 hands . These surgeries were performed on an outpatient basis . After application of a local anesthetic, a microsurgical technique using a 2-cm longitudinal incision that did not cross the wrist flexion crease was accomplished . In five patients the recurrent thenar branch exited through the middle or ulnar portion of the ligament and this branch was preserved in all five . Perioperative complications included stitch abscesses in nine hands (2%), which were managed on an outpatient basis; deep wound infections occurred in three hands (0.5%) and these patients were admitted for intravenous antibiotic administration and wound care . One steroid-dependent patient suffered wound dehiscence due to a fall and the wound was primarily repaired . One patient required a second minor procedure to remove a retained suture . Two patients developed "trigger finger" 6 months postoperatively . The mean time until return to work for those patients not receiving Workers' Compensation was 3 weeks and for those receiving Workers' Compensation it was 6.5 weeks . Complete disappearance of painful dysesthesias occurred in 431 (89%) of 482 patients . Marked improvement occurred in another 33 (7%) patients, yielding an overall improvement rate of 96% . Motor improvement was noted in 438 (96%) of 454 patients with preoperative motor weakness . Bilateral symptoms resolved on the contralateral side following unilateral surgery in seven patients . Fifteen patients (12 of whom were receiving Workers' Compensation) experienced persistent dysesthesias and/or incision pain and did not return to work . An additional eight procedures were performed in patients who had previously undergone surgery at another institution; four showed no evidence of their transverse carpal ligament being sectioned . Five of the eight patients undergoing reexploration noted postoperative improvement in their symptoms . Finally, 14 (3%) patients presented 1 to 5 years postsurgery with thenar/hypothenar pain . These patients have responded to local steroid injections and are being followed by a hand surgeon . The reimbursement of the surgeon's fee is 253.00 dollars from Medicaid, 360.00 dollars from Medicare, and 560.00 dollars from preferred provider insurance . The mean total time in the outpatient operating room is 35 to 40 minutes . The outcome and time to return to work are equal, if not superior, to those reported for endoscopic CTR surgery . Microsurgical CTR is thought to be safer and probably more cost-effective.

Dis Manag Advis, 2004 Mar, 10(3), 27 - 30
New guidelines for sinusitis target prescribing practices; The impact of sinus computed tomography on treatment decisions for chronic sinusitis; Department of Radiology, University of Washington, Seattle 98195-7115, USA . anzai@u.washington.edu

OBJECTIVES: To determine the impact of sinus computed tomography (CT) on treatment decisions by otolaryngologists and to explore the factors leading to choice of surgical treatment for patients suspected of having chronic sinusitis . DESIGN: Prospective cohort study . SETTING: A tertiary academic medical center . PATIENTS: Questionnaires were administered to 3 otolaryngologists in a tertiary academic institution regarding diagnosis and treatment decisions in 27 patients suspected of having chronic sinusitis, before and after they reviewed sinus CT scans . MAIN OUTCOME MEASURES: The dichotomous decisions regarding surgical or nonsurgical treatment and the agreement of treatment decisions among surgeons were evaluated . The factors strongly influencing surgeons' treatment decisions regarding patients selected for surgery were also determined . RESULTS: The dichotomous treatment decisions were changed in one third of patients (9 of 27) after the sinus CT scans were reviewed . The agreement of treatment decisions among the 3 surgeons was markedly improved after they reviewed sinus CT scans . The factors favorably influencing surgical treatment were obstruction of the ostiomeatal complex on CT and concordance of CT abnormality with a patient's symptoms . Lund-Mackay stage, symptoms, and corticosteroid or antibiotic use were not significant predictors . CONCLUSIONS: Despite the common belief that treatment decisions for chronic sinusitis should be solely based on clinical grounds, with sinus CT providing only anatomic detail before surgery, our study indicates that the decision to perform surgery was altered by CT in a substantial portion of the patients . In our preliminary study, CT increased the tendency to elect surgical treatment by all 3 surgeons.

Rev Hist Pharm (Paris), 2003, 51(340), 611 - 24
{When blood and meat were drugs}; Bonnemain B; When one look at pharmaceutical advertising and trademarks at the beginning of the 20th century, several of them emphasize the interest of pharmaceutical specialties based on animal blood . This fashion goes back to Fuster's work in 1865 on tuberculosis, but also to Deschiens, Catillon, Adrian and mainly Richet . This interest for blood derivatives in therapy will progressively disappear after teh Second World war and with antibiotic discovery . Consequently, it has been a century of glory for these specialties that seem strange today in the context of HIV and ESB issues . But some of these research will be the basis for modern works on erythropoetin (the famous EPO).

Mol Ther, 2004 Apr, 9(4), 577 - 86
Cellular immunotherapy for follicular lymphoma using genetically modified CD20-specific CD8+ cytotoxic T lymphocytes; Wang J et al.; Humoral immunotherapy using the monoclonal anti-CD20 antibody rituximab induces remissions in approximately 60% of patients with relapsed follicular lymphoma; however, most patients eventually relapse despite continued expression of CD20 on lymphoma cells . We have hypothesized that cellular immunotherapy targeting CD20(+) cells might provide a more effective mechanism for eliminating lymphoma cells than anti-CD20 antibodies and are therefore investigating the utility of cytotoxic T lymphocytes (CTL) genetically modified to target the CD20 antigen . Peripheral blood mononuclear cells were activated with anti-CD3 antibody (OKT3) and recombinant human interleukin-2 and electroporated with a plasmid containing a CD20-specific scFvFc:zeta chimeric T cell receptor gene and a neomycin phosphotransferase gene (neo(R)) . Transfected cells were selected using the antibiotic G418 and cloned by limiting dilution . Using this approach, we have generated CD8(+) CTL clones with CD20-specific cytotoxicity, which specifically lysed CD20(+) target cells, including actual tumor cells from patients with follicular lymphoma, small lymphocytic lymphoma, splenic marginal zone lymphoma, diffuse large B cell lymphoma, and chronic lymphocytic leukemia . The CTL clones have been expanded to numbers sufficient for therapy ( approximately 10(9) cells) . Our data indicate the feasibility of generating and expanding CD20-specific CTL and, for the first time, demonstrate that such CTL exhibit specific cytotoxicity against actual tumor cells isolated from patients with a variety of B lymphoid malignancies . In view of these promising findings, a Phase I clinical trial for relapsed follicular lymphoma is being initiated.

Curr Opin Clin Nutr Metab Care, 2004 Jan, 7(1), 21 - 6
Prevention of food-drug interactions with special emphasis on older adults; McCabe BJ; PURPOSE OF THE REVIEW: Adverse drug interactions may be the fourth leading cause of death in hospitalized patients . In children and older adults undetected food-drug interactions may lead to serious morbidity and mortality and be misdiagnosed as chronic disease progression . Recent recognition of the effects of certain foods on many drugs metabolized by CYP450 families or drugs susceptible to chelation and adsorption have increased awareness for prevention of food-drug interactions . RECENT FINDINGS: Polypharmacy, self-medications with non-prescription drugs including herbal remedies, dietary/nutritional supplements, fortified foods, and polymorphism in drug metabolism increase the need to consider food-drug interactions . Improved food processing and analysis have led to overall decreased risk in monoamine oxidase inhibitor regimens with counseling . Drugs may create submarginal nutrient deficiencies with serious consequences, such as diuretics contributing to thiamin deficiency and further cardiac failure . Foods may contain compounds that lead to therapeutic failure, such as calcium-fortified foods producing therapeutic failure and promoting resistance in antibiotic therapy . Poor nutritional status can lead to poor health outcomes . SUMMARY: Prevention of adverse events from food-herb-drug interactions requires clinical monitoring in high-risk regimens and populations . Nutritional status has an important impact on the quality of life as well as appropriate responses to drug therapy . Both diet-drug histories and counseling are needed . As new foods and drugs emerge and more self-medication is promoted, research in the prevention of food-drug interactions is needed.

J Bacteriol, 2004 May, 186(9), 2567 - 75
Identification of PimR as a positive regulator of pimaricin biosynthesis in Streptomyces natalensis; Anton N et al.; Sequencing of the DNA region on the left fringe of the pimaricin gene cluster revealed the presence of a 3.6-kb gene, pimR, whose deduced product (1,198 amino acid residues) was found to have amino acid sequence homology with bacterial regulatory proteins . Database comparisons revealed that PimR represents the archetype of a new class of regulators, combining a Streptomyces antibiotic regulatory protein (SARP)-like N-terminal section with a C-terminal half homologous to guanylate cyclases and large ATP-binding regulators of the LuxR family . Gene replacement of pimR from Streptomyces natalensis chromosome results in a complete loss of pimaricin production, suggesting that PimR is a positive regulator of pimaricin biosynthesis . Gene expression analysis by reverse transcriptase PCR (RT-PCR) of the pimaricin gene cluster revealed that S . natalensis DeltaPimR shows no expression at all of the cholesterol oxidase-encoding gene pimE, and very low level transcription of the remaining genes of the cluster except for the mutant pimR gene, thus demonstrating that this regulator activates the transcription of all the genes belonging to the pimaricin gene cluster but not its own transcription.

Aust Vet J, 2004 Jan-Feb, 82(1-2), 48 - 51
Generalised granulomatous disease in a horse; Axon JE et al.; A 6-year-old gelding was referred with a 3-month history of recurrent fever, inappetance, lethargy and weight loss . On clinical examination major findings were depression, thin condition, thrombophlebitis, nodules on the scrotal skin, leukocytosis, hyperfibrinogenaemia and hyperglobulinaemia . Pleural fluid and areas of lung consolidation were seen on ultrasonographic examination of the thorax . A diagnosis of chronic respiratory disease was made . Initially there was a response to antibiotic therapy but the horse was presented 3 months later with continued weight loss, recurrent fever and multifocal skin lesions, characterised by scales, crusts and nodules, affecting the nasal bridge, jugular grooves, ventral neck, withers, scrotum, prepuce, and medial gaskins . Histological evaluation of skin biopsies indicated a granulomatous reaction . On ultrasonographic examination of the thorax multiple hypoechoic lesions consistent with granulomas were seen in both lungs . A diagnosis of generalised granulomatous disease was made . The horse was euthanased at the owner's request . On necropsy examination the main findings were multiple nodules of fibrotic granulomatous inflammation in the lung, heart, liver, gastrointestinal tract and mesenteric lymph nodes, supporting the diagnosis of generalised granulomatous disease.

J Periodontol, 2004 Mar, 75(3), 453 - 63
Subantimicrobial dose doxycycline efficacy as a matrix metalloproteinase inhibitor in chronic periodontitis patients is enhanced when combined with a non-steroidal anti-inflammatory drug; Lee HM et al.; BACKGROUND: Administration of subantimicrobial dose doxycycline (SDD) to chronic periodontitis (CP) patients has repeatedly been found to reduce mammalian collagenase and other matrix metalloproteinase (MMP) activity in gingival tissues and crevicular fluid, in association with clinical efficacy, without the emergence of antibiotic-resistant bacteria either orally or extra-orally . More recently, SDD adjunctive to repeated mechanical debridement resulted in dramatic clinical improvement in patients (>50% smokers) with generalized aggressive periodontitis . As an additional pharmacologic approach, non-steroidal anti-inflammatory drugs (NSAIDs) can reduce gingival inflammation and alveolar bone resorption, at least under experimental conditions . In the current study, we determined the effect of administering a combination (combination) of these two host-modulating drugs (SDD plus low-dose NSAID) to CP patients, on selected neutral proteinases in gingiva, enzymes believed to mediate periodontal breakdown . Earlier preliminary studies in humans with bullous pemphigoid, which is also associated with excessive levels of host-derived proteinases including MMPs, indicated improved clinical efficacy of combination therapy . METHODS: Nineteen CP patients, scheduled for mucoperiosteal flap surgery bilaterally in the maxillary arch, were randomly distributed into three experimental groups administered either 1) low-dose flurbiprofen (LDF) alone, 50 mg q.d.; 2) SDD (20 mg b.i.d.) alone; or 3) a combination of SDD plus LDF (combination) . The gingival tissues were biopsied during surgery from right and left maxillary posterior sextants, before and after a 3-week regimen of medication, respectively . The tissues were then extracted, the extracts partially purified, then analyzed for the endogenous proteinase inhibitor, alpha1-PI, and its breakdown product, and for host-derived matrix metalloproteinases (i.e., collagenases, gelatinases) and neutrophil elastase activities . RESULTS: Short-term therapy with SDD alone produced a significant reduction and LDF alone produced no reduction in host-derived neutral proteinases . However, the combination therapy produced a statistically significant synergistic reduction of collagenase, gelatinase, and serpinolytic (alpha1-PI degrading) activities (69%, 69%, and 75% reductions, respectively) and a lesser reduction of the serine proteinase, elastase (46%) . CONCLUSIONS: Consistent with previous studies on animal models of chronic destructive disease (e.g., rheumatoid arthritis), the SDD and NSAID combination therapy synergistically suppressed MMP and other neutral proteinases in the gingiva of CP patients . A mechanism, suggested by earlier animal studies, involves the NSAID, in the combination regimen, increasing the uptake of the tetracycline-based MMP inhibitor in the inflammatory lesion, thus synergistically enhancing the efficacy of this medication.

Mol Genet Genomics, 2004 Jun, 271(5), 595 - 602 Epub 2004 Apr 16.
A multicopy vector system for genetic studies in Mucor circinelloides and other zygomycetes; Appel KF et al.; Transformation of Mucor circinelloides is routinely achieved by using a plasmid containing the wild-type leuA gene to complement the leucine requirement of an auxotrophic host strain . As is the case for other zygomycetes, the transforming DNA is usually not integrated into the genome of M . circinelloides, but is maintained as an autonomously replicating plasmid . However, even under selective conditions, the plasmid is segregationally unstable, resulting in a rather low number of cells carrying the plasmid . We report here on a new transformation vector based on a dominant selection marker conferring resistance to geneticin, which allows for plasmid maintenance in high copy numbers . The vector was also used to transform Mucor rouxii and Rhizomucor pusillus, and should therefore be a valuable tool for gene expression studies in zygomycetes . The functionality and regulatory properties of the promoter of the M . circinelloides gpd1 gene (which codes for glyceraldehyde-3P-dehydrogenase) were demonstrated in R . pusillus using geneticin selection . In this work, we have also determined the molecular basis of the Leu(-) phenotype of the M . circinelloides host strain R7B . The leucine requirement is due to a single point mutation in the leuA gene that results in the replacement of a glutamic acid by a lysine residue.

Clin Exp Immunol, 2004 May, 136(2), 215 - 23
Transfer factors as immunotherapy and supplement of chemotherapy in experimental pulmonary tuberculosis; Fabre RA et al.; Problems of logistics, compliance and drug resistance point to an urgent need for immunotherapeutic strategies capable of shortening the current six month antibiotic regimens used to treat tuberculosis . One potential immunotherapeutic agent is transfer factors . Transfer factors (TF) are low molecular weight dialysable products from immune cells which transmit the ability to express delayed-type hypersensitivity (DTH) and cell mediated immunity from sensitized donors to nonimmune recipients . In this study we determined the efficiency of TF as immunotherapy to treat experimental tuberculosis . When BALB/c mice are infected via the trachea with Mycobacterium tuberculosis H37Rv there is an initial phase of partial resistance dominated by Th-1 type cytokines plus tumour necrosis factor-alpha (TNFalpha) and the inducible isoform of nitric oxide synthase (iNOS), followed by a phase of progressive disease characterized by increasing expression of IL-4, diminished expression of TNFalpha and iNOS, and low DTH . Animals in this late progressive phase of the disease (day 60) were treated with different doses of TF (one injection per week) obtained from spleen cells when the peak of immune protection in this animal model is reached (day 21), or with different doses of TF from peripheral leucocytes of PPD + healthy subjects . We show here that the treatment with murine or human TF restored the expression of Th-1 cytokines, TNFalpha and iNOS provoking inhibition of bacterial proliferation and significant increase of DTH and survival . This beneficial effect was dose dependent . Interestingly, murine TF in combination with conventional chemotherapy had a synergistic effect producing significant faster elimination of lung bacteria loads than chemotherapy alone.

Dis Colon Rectum, 2004 Jun, 47(6), 864 - 8 Epub 2004 Apr 19.
Outcome after transperineal mesh repair of rectocele: a case series; Mercer-Jones MA et al.; PURPOSE: This study was designed to establish the safety and efficacy of transperineal mesh repair in patients with obstructed defecation caused by rectocele . METHODS: Between 1998 and 2002, 24 consecutive females with symptomatic rectocele were retrospectively reviewed after mesh repair of rectocele . Two patients had inadvertent rectal perforation during operation and had no mesh implantation . Of the remaining 22 patients, 14 had a prolene mesh implanted, and 8 had a Vipro II mesh implanted . Median age at the time of presentation was 55 (range, 28-66) years . Patients were selected for operation based on clinical and evacuation proctogram findings . All patients complained of incomplete rectal evacuation, and the majority complained of excessive straining, constipation, and the need for vaginal/perineal digital pressure to aid defecation . Patients were followed up in clinic at six weeks, and a telephone questionnaire was performed at a median time of 12.5 (range, 3-47) months . Functional/objective outcomes were assessed for the following five symptoms preoperatively and postoperatively: excessive straining, incomplete evacuation, perineal/vaginal digital pressure, vaginal bulging, and constipation (always, usually, occasionally, never) . Subjective outcomes were assessed as excellent, good, moderate, or poor . In addition, patients were asked about preexisting and postoperative dyspareunia . RESULTS: Objective outcomes based on symptoms showed an improvement in two or more symptoms in 20 patients (91 percent) . For all symptoms, there was a significant reduction in mean values after repair . Subjective outcomes showed that 17 patients (77 percent) had a moderate/good/excellent result . Patients with abnormal preoperative colonic transit marker studies did as well as those who had no transit studies performed or those who had normal studies . Patients who did not vaginally digitate did as well as those who did not digitate . Only one patient complained of new onset dyspareunia . Two patients with sphincter defects on endoanal ultrasound had a sphincteroplasty performed (1 prerectocele repair and 1 at the same time) . There were two superficial wound infections and one deep infection . All infections responded to antibiotic therapy . No mesh has been removed . Semiabsorbable mesh repair was superior to nonabsorbable mesh repair . CONCLUSIONS: Transperineal mesh repair of symptomatic rectocele is a safe technique that avoids the anal dilation and sphincter injury associated with endorectal repair . Objective and subjective results are good in the majority of patients, although a longer follow-up is required to confirm no deterioration.

J Toxicol Clin Toxicol, 2004, 42(1), 85 - 8
Accidental poisoning with autumn crocus; Gabrscek L et al.; We describe a case of a 43-yr-old female with severe multiorgan injury after accidental poisoning with Colchicum autumnale, which was mistaken for wild garlic (Allium ursinum) . Both plants grow on damp meadows and can be confused in the spring when both plants have leaves but no blossoms . The autumn crocus contains colchicine, which inhibits cellular division . Treatment consisted of supportive care, antibiotic therapy, and granulocyte-directed growth factor . The patient was discharged from the hospital after three weeks . Three years after recovery from the acute poisoning, the patient continued to complain of muscle weakness and intermittent episodes of hair loss.

Eur Respir J, 2004 Apr, 23(4), 649 - 50
G-CSF enables completion of tuberculosis therapy associated with iatrogenic neutropenia; Cormican LJ et al.; Neutropenia is a rare complication of anti-tuberculous therapy and is usually due to a single agent, most frequently isoniazid . The current case describes a previously healthy immunocompetent patient with tuberculosis of the lymph nodes who developed neutropenia due to a number of first line antibiotics (rifampicin, isoniazid and ethambutol) and streptomycin when introduced in combination and individually thus resulting in repeated treatment disruption . The introduction of twice-weekly subcutaneous granulocyte-colony stimulating factor to correct iatrogenic neutropenia facilitated the continuation and eventual completion of therapy without adverse effect . This is the first description of the use of granulocyte-colony stimulating factor to correct iatrogenic neutropenia due to anti-tuberculous antibiotics and the second description of the occurrence of iatrogenic neutropenia to more than anti-tuberculous antibiotic in an individual.

J Food Prot, 2004 Apr, 67(4), 799 - 804
A comparison of three methods for the isolation of Arcobacter spp . from retail raw poultry in Northern Ireland; Scullion R et al.; Recent evidence suggests that arcobacters, especially Arcobacter butzleri, are potential foodborne pathogens, but standardized detection methods have yet to be established . A study was undertaken to determine which of three isolation methods was the most effective for the isolation of Arcobacter spp . from fresh raw poultry . Methods 1 was microaerobic and involved a membrane filtration step followed by plating onto blood agar . Method 2 was also microaerobic and involved enrichment and plating media containing a five-antibiotic cocktail . Method 3 was aerobic and was based on enrichment in a charcoal-based broth containing two antibiotics . Retail poultry samples (n = 50) were obtained from supermarkets in Northern Ireland; the European Community license number was recorded to ensure sample diversity . Presumptive arcobacters were identified using genus-specific and species-specific primers . Methods 1 resulted in the lowest recovery of arcobacters (28% of samples positive) . The detection rate for method 2 (68%) was higher than that for method 3 (50%), but the difference was not significant (P > 0.05) . Modification of method 3 by plating the enrichment broth at 24 h, as well as at 48 h, increased recovery to 68% . Use of methods 2 and 3 together increased the number of positive samples detected by approximately 25% compared with use of either method alone . A . butzleri was the most commonly isolated species using all methods . Method 3 detected Arcobacter cryaerophilus in more samples (n = 3) than did method 1 and 2 (n = 1) . Arcobacter skirrowii was detected by only method 3 (n = 1) . In terms of sensitivity, ease of use, and diversity of species recovered, modified method 3 was the overall method of choice.

Int J Epidemiol, 2004 Apr, 33(2), 253 - 60
Commentary: the 1944 patulin trial: the first properly controlled multicentre trial conducted under the aegis of the British Medical Research Council; Chalmers I et al.; The 1948 report of the British Medical Research Council's randomized trial of streptomycin for pulmonary tuberculosis is widely regarded as marking the beginning of the modern history of controlled clinical trials . Four years earlier, however, a methodologically sophisticated multicentre trial conducted under the aegis of the Medical Research Council was reported, which assessed the effects of the antibiotic patulin on the course of common colds . Philip D'Arcy Hart and Joan Faulkner (later Joan Doll) were the secretary and assistant secretary, respectively, to the committee overseeing the trial, and they clearly recognized the importance of preventing foreknowledge of allocations from those admitting patients to the study . To do this and to 'muddle people up', they and Ruth D'Arcy Hart devised a scheme involving the use of two patulin groups and two placebo groups, allocating patients to one of these four groups using strict rotation . Philip D'Arcy Hart believes that this study has been overshadowed by the celebrated streptomycin trial (for which he was also secretary to the oversight committee) because no beneficial effect of patulin was detected, and because the report of the streptomycin trial referred to the use of random sampling numbers to generate the allocation schedule . This article makes clear why we agree with Philip D'Arcy Hart that the 1944 patulin trial deserves wider recognition as the first well controlled, multicentre clinical trial to have been conducted under the aegis of the British Medical Research Council . This status is reflected in the International Journal of Epidemiology's reproduction of the full text of the trial report in this issue of the journal.

Comp Biochem Physiol B Biochem Mol Biol, 2004 Apr, 137(4), 455 - 61
Biosynthesis and dietary uptake of polyunsaturated fatty acids by piezophilic bacteria; Fang J et al.; The biochemistry of piezophilic bacteria is unique in that piezophiles produce polyunsaturated fatty acids (PUFAs) . A pertinent question is if piezophilic bacteria synthesize PUFA de novo, through dietary uptake, or both . This study was undertaken to examine the biosynthesis and cellular uptake of PUFAs by piezophilic bacteria . A moderately piezophilic (Shewanella violacea DSS12) and two hyperpiezophilic bacteria (S . benthica DB21MT-2 and Moritella yayanosii DB21MT-5) were grown under 50 MPa (megapascal) and 100 MPa, respectively, in media containing marine broth 2216 supplemented with arachidonic acid (AA, sodium salt) and/or antibiotic cerulenin . There was active uptake and cellular incorporation of AA in the hyperpiezophilic bacteria DB21MT-2 (14.7% of total fatty acids) and DB21MT-5 (1.4%), but no uptake was observed in DSS12 . When cells were treated with cerulenin, all three strains incorporated AA into cell membranes (13-19%) . The biosynthesis of monounsaturated fatty acids was significantly inhibited (10-37%) by the addition of cerulenin, whereas the concentrations of PUFAs increased by 2-4 times . These results suggest that piezophilic bacteria biosynthesize and/or incorporate dietary polyunsaturated fatty acids that are important for their growth and piezoadaptation . The significance of these findings is also discussed in the context of phenotypic classification of piezophiles.

Farmaco, 2004 Apr, 59(4), 289 - 96
Interaction of amphotericin B and its low toxic derivative, N-methyl-N-D-fructosyl amphotericin B methyl ester, with fungal, mammalian and bacterial cells measured by the energy transfer method; Szlinder-Richert J et al.; Amphotericin B (AMB) derivative, N-methyl-N-D-fructosyl amphotericin B methyl ester (MFAME) retains the broad antifungal spectrum and potency of the parent antibiotic, whereas its toxicity towards mammalian cells is reduced by about two orders of magnitude . The purpose of this work was to find out whether the differences observed in the toxicity of MFAME and native AMB are due to the differential drugs affinity to fungal and mammalian cell membranes . Comparative studies on AMB and MFAME biological activity and their affinity to fungal, mammalian and bacterial cells were performed . The interaction of AMB and MFAME with cells have been studied by fluorescence method based on the energy transfer between membrane fluorescent probe (donor) and the polyenic chromophore of the antibiotic (acceptor) simultaneously present in the cell membrane . The amount of the antibiotic bound to cells was indicated by the extent of fluorescence quenching of 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) or 1,6-diphenyl-1,3,5-hexatriene (DPH) by polyenic chromophore of the antibiotic . The results obtained indicate that binding extent and characteristics for both antibiotics are comparable in the three types of cells studied . Dramatically lower toxicity of MFAME as compared to AMB towards mammalian cells is not related to the antibiotic-cell affinity, but rather to different consequences of these interactions for cells, reflected in membrane permeabilization . MFAME is definitely less effective than parent AMB in the permeabilizing species formation in mammalian cell membrane.

Aust Vet J, 2003 Mar, 81(3), 136 - 9
Catheters: a review of the selection, utilisation and complications of catheters for peripheral venous access; Tan RH et al.; Intravenous catheters are used for the administration of medications and fluids and are an integral part of veterinary practice . The aim of catheter use is to optimise administration of medication and minimise complications such as thrombus formation, thrombophlebitis and sepsis . Catheters made from teflon are less flexible, less durable and stimulate more tissue reaction than polyurethane or silicon . However silicon catheters are more expensive and complicated to insert . Generally, for veterinary practice, the biostability and cost of polyurethane catheters make them preferable for short and long-term use . The smallest diameter catheter should be selected to minimise internal vessel wall contact and irritation without compromising medication delivery . The site of insertion varies with individual preference, vessel access and patient compliance . The jugular, cephalic, saphenous, ear, lateral thoracic and subcutaneous abdominal veins are accessible . Hair removal and a thorough aseptic skin preparation should be performed prior to catheter insertion . Daily maintenance is required to detect complications and maximise catheter longevity . Potential complications include thrombus formation, thromboembolism, bacterial colonisation and septicaemia, blood loss and air embolism . Permanent or transient skin dwelling bacteria are commonly isolated if sepsis occurs . The development of novel antiseptic and antibiotic impregnated catheters may reduce the complications associated with catheter infection in the future.

Cas Lek Cesk, 2004, 143(2), 114 - 6
{Infectious endocarditis as a complication of cardiac pacemakers requiring emergency removal of the stimulating electrode}; Mika M et al.; Case report describes a patient with permanent pacemaker (implanted in childhood) who has developed infectious endocarditis with bacterial vegetation on the stimulation electrode while no febrile condition occurred and laboratory tests showed no inflammation . The course of the disease was affected by the previous inappropriate outpatient treatment of an infection in the suture after the pacemaker exchange . It should be noted that echocardiographic examination was essential for both the diagnostics and the choice of strategy . The therapeutic approach consisted of the combination of long-term antibiotic therapy and the explantation of the infected stimulation system . As it was not possible to accomplish by endovasal methods only, cardiosurgery for extraction of the lead was chosen.

Mikrobiol Z, 2003 Nov-Dec, 65(6), 24 - 30
{Synthesis of carotenoids by mutant strains of Streptomyces globisporus 1912}; Matseliukh BP et al.; Landomycin-deficient mutants (24) were obtained under the effect of nitrosoguanidine on the strains 3-1 and RSp2 of Streptomyces globisporus 1912, high active procedures of polyketide antibiotic landomycin E . Two strains of these mutants produced red and one strain--yellow pigments . The absorption spectra of the pigments purified by means of thin layer chromatography were characterized by three maxima of absorption of acetone 446-448, 472-474 and 501-507 nm resembling the same characteristic of lycopene . The Rf values of isolated pigments and lycopene do not differ between themselves . The corn medium is more optimal for lycopene synthesis by strains of S . globisporus 1912 in comparison with soy one . The highly active mutants synthesized 2 mg of lycopene per 1 g of dry biomass . High frequency of spontaneous mutability of lycopene production of isolated strains can be explained by the localization of gene cluster for carotenoid biosynthesis on the one end of linear chromosome, where genetic rearrangements often take place (amplifications, deletions, recombination) because of the presence of terminal inverter DNA repetitions.

Am Heart J, 2004 Apr, 147(4), 599 - 604
Novel approaches to clinical trials: device-related infections; Califf RM et al.; The explosive growth in the use of cardiac devices and the continued large number of thoracic operations produce a significant number of costly infectious complications . These infections represent a leading cause of death and disability after device implantation or surgery . Unfortunately, few objective data are available to validate the clinical epidemiology of surgical and device-related infections, and although the number of randomized trials is increasing, too few have tested strategies for prophylaxis or treatment, particularly in the cardiac arena . Because of the expected increase in invasive vascular procedures and device implantations, it is timely to consider innovative approaches to clinical research that will hasten the translation of effective therapeutic strategies and technologies into clinical practice . Because of the multidisciplinary nature of the care of patients undergoing thoracic surgery or device implantation, bringing together existing networks and several arms of the Federal government could rapidly advance this field to provide a definitive base of evidence to guide clinical practice and improve clinical outcomes . The remainder of the articles in this supplement discuss specific issues on the diagnosis and treatment of device-related or surgical infection . The purpose of this manuscript is to discuss issues about the design of studies and their organization.

Int J Epidemiol, 2004 Feb, 33(1), 116 - 20
Nitrogen dioxide is not associated with respiratory infection during the first year of life; Sunyer J et al.; BACKGROUND: Nitrogen dioxide (NO(2)) has been related to respiratory infections in experimental studies but its role remains controversial in general population studies of children . We aim to assess the association between indoor NO(2) and lower respiratory tract infections (LRTI) during the first year of life in a multicentre prospective cohort study . METHODS: Children (n = 1611) were recruited prior to birth for the Asthma Multicentre Infants Cohort Study (AMICS) . Three concurrent cohorts (Ashford, Kent {UK}; Barcelona city, and Menorca Island {Spain}) followed the same research protocol . NO(2) was measured with passive diffusion tubes placed in the living room for 2 weeks when infants were approximately 3 months old . Doctor-diagnosed LRTI during the first year of life (as well as antibiotic use) were measured by questionnaire, and in Ashford validated by the examination of clinical records . In Barcelona, direct measurements using nasopharyngeal lavage and cultures within a continuous surveillance system were done . RESULTS: The cumulative rates of LRTI (39% in Ashford, 28% in Barcelona, and 45% in Menorca) were unrelated to NO(2) levels (corresponding medians 6, 46, and 12 ppb, respectively) in all three centres (all odds ratios being around 1) . Similarly, the rates of LRTI in Barcelona measured with the continuous record showed no association with NO(2) (all rate ratios being below 1) . In addition, there was no association between rate of antibiotics courses per year per child (2.4 in Ashford, 1.7 in Barcelona, 0.9 in Menorca) and NO(2) levels . CONCLUSIONS: Indoor NO(2) at current levels does not seem to be involved in increasing respiratory infections by itself in infants, suggesting that the effects observed in studies on outdoor air are probably due to other copollutants.

Int J STD AIDS, 2004 Apr, 15(4), 275 - 6
Symptomatic trichomoniasis, metronidazole allergic and pregnant--a management dilemma; Lomax NJ et al.; A case of persistent Trichomonas vaginalis (TV) in a pregnant, metronidazole-allergic woman is described . This case posed a management dilemma as untreated TV has been associated with adverse pregnancy outcomes but antibiotic desensitization is potentially dangerous during pregnancy.

Eur J Epidemiol, 2004, 19(2), 163 - 9
Surgical site infection of 7301 traumatologic inpatients (divided in two sub-cohorts, study and validation): modifiable determinants and potential benefit; Herruzo-Cabrera R et al.; The widespread use of peri-surgical chemoprophylaxis is decreasing the incidence of surgical site infection in Traumatology, which nevertheless remains as a problem amenable to further reduction . We have tried to identify modifiable determinants of the avoidable incidence of surgical site infection, and to estimate the potential benefit from implementing adequate measures targeting those determinants . In a firts sub-cohort of 5320 traumatologic patients with a post-surgical stay of more than 2 days, in Madrid's La Paz Hospital, between 1991 and 1996 . The epidemiological surveillance was prospective during their hospital stay but also includes data on readmissions due to infection so as to analyse the actual incidence of surgical site infection, both before and after discharge . Bivariate and multivariate (multiple logistic regression model) analyses of risk factors for surgical site infections have been performed . In this sub-cohort, 212 patients (3.9%) suffered some type of nosocomial infection . The incidence of surgical site infection before discharge in cases of clean surgery was 1.6%, rising to 2% when cases readmitted for infection after discharge were considered . The multivariate analysis of risk factors for surgical site infection identified the following: contaminated ('dirty') surgery (OR: 10.5), inadequate chemoprophylaxis (OR: 1.5) and a pre-surgical stay of more than 4 days (OR: 1.6) . Next, a second sub-cohort, consisting of 1981 patients, treated between 1997 and 1999, was analysed to validate the results of the first multivariate analysis . The validation model (and the global cohort with 7301 patients) corroborates the importance of the same three factors . Last, we calculated that controlling two modifiable factors, pre-surgical stay and peri-surgical chemoprophylaxis, could avoid 56% of surgical site infections.

Pharmacoepidemiol Drug Saf, 1996 Nov, 5(6), 399 - 407
The safety of ranitidine bismuth citrate in controlled clinical studies; Pipkin GA et al.; Ranitidine bismuth citrate (Pylorid, Tritec) is a novel drug which heals peptic ulcers and when co-prescribed with either clarithromycin or amoxycillin eradicatesHelicobacter pylori . In controlled clinical studies it was well-tolerated when given alone or when co-prescribed with either antibiotic . Data from 20 clinical studies are reported in this analysis of safety with almost 5000 patients having received ranitidine bismuth citrate (200, 400, or 800 mg twice daily) . The incidence of adverse events reported with this new drug, either alone or with an antibiotic, was not different from or lower than in patients given placebo and was independent of the dose of ranitidine bismuth citrate tested . Most commonly reported events (>1% of patients) were upper respiratory tract infection, constipation, diarrhoea, nausea and vomiting, dizziness, and headache, the latter being the only event reported by >2% of patients who received ranitidine bismuth citrate alone . Adverse events considered by the clinical investigator to be adverse reactions occurred with a similar frequency amongst patients given ranitidine bismuth citrate (8%), ranitidine hydrochloride (6%), or placebo (6%) . The incidence of adverse reactions was greater when co-prescribed with amoxycillin (11%) or clarithromycin (20%) although it was not different from that noted with the antibiotics alone . Serious adverse events were reported in similar proportions of patients given placebo, ranitidine bismuth citrate alone or with an antibiotic, and ranitidine hydrochloride (range: <1-2%) . The safety profile of ranitidine bismuth citrate was thus comparable to that of ranitidine hydrochloride (Zantac), a drug with a well-established record of safety in clinical use.

J Infect Dis, 2004 Apr 15, 189(8), 1497 - 505 Epub 2004 Mar 31.
Rapid sequence-based identification of gonococcal transmission clusters in a large metropolitan area; Martin IM et al.; In large metropolitan areas, which typically have the highest rates of gonorrhea, the identification of chains of transmission by use of partner notification is problematic, and there is an increasing interest in applying molecular approaches, which would require new discriminatory high-throughput procedures for recognizing clusters of indistinguishable gonococci, procedures that identify local chains of transmission . Sequencing of internal fragments of 2 highly polymorphic loci, from 436 isolates recovered in London during a 3-month period, identified clusters of antibiotic-resistant and antibiotic-susceptible isolates with indistinguishable genotypes, the vast majority of which were also identical or closely related by other methods, and defined groups of individuals who typically had similar demographic characteristics . This discriminatory sequence-based approach produces unambiguous data that easily can be compared via the Internet and appears to be suitable for the identification of linked cases of gonorrhea and the timely identification of transmission of antibiotic-resistant strains, even within large cities.

Int J Pharm, 2004 Apr 15, 274(1-2), 261 - 8
Behaviour of an injectable calcium phosphate cement with added tetracycline; Ratier A et al.; A calcium phosphate cement containing an antibiotic can be used for filling bone defects and to ensure local antibiotherapy . A calcium phosphate cement (already marketed under the name of Cementek can become injectable thanks to the addition of silicone . For dental applications, the behaviour of this injectable cement with added tetracycline was investigated . The tetracycline hydrochloride does not allow maturation of the cement: the tetracycline has to be treated with a calcium sulphate solution . The treated tetracycline (TTC) allowed maturation of the cement towards hydroxyapatite . But the setting time was longer and the mechanical properties decreased . Study in a continuous flow cell showed that the tetracycline is released in a continuous manner: thus, after 6 days, 60% of the antibiotic was released into the surrounding medium.

Proc Natl Acad Sci U S A, 2004 Mar 30, 101(13), 4608 - 13 Epub 2004 Mar 18.
Mycobacterial polyketide-associated proteins are acyltransferases: proof of principle with Mycobacterium tuberculosis PapA5; Onwueme KC et al.; Mycobacterium tuberculosis (Mt) produces complex virulence-enhancing lipids with scaffolds consisting of phthiocerol and phthiodiolone dimycocerosate esters (PDIMs) . Sequence analysis suggested that PapA5, a so-called polyketide-associated protein (Pap) encoded in the PDIM synthesis gene cluster, as well as PapA5 homologs found in Mt and other species, are a subfamily of acyltransferases . Studies with recombinant protein confirmed that PapA5 is an acyltransferase {corrected} . Deletion analysis in Mt demonstrated that papA5 is required for PDIM synthesis . We propose that PapA5 catalyzes diesterification of phthiocerol and phthiodiolone with mycocerosate . These studies present the functional characterization of a Pap and permit inferences regarding roles of other Paps in the synthesis of complex lipids, including the antibiotic rifamycin.

J Biomater Appl, 2004 Apr, 18(4), 279 - 89
A covalent method of gentamicin bonding to silica supports; Ginalska G et al.; Results of a novel method of covalent bonding of an antibiotic (gentamicin) to silica bead supports are shown . Gentamicin was immobilized to four types of matrix: silica gel and porous glass beads activated by either silanization (APTES) or by adhesively bound keratin (with immobilization yield ranging from 36.5 to 91%) . Gentamicin was immobilized to the supports after opening its carbohydrate ring in the molecule . This method of gentamicin activation before the immobilization process did not inhibit its antibiotic activity . The four gentamicin-containing immobilized preparations were stable, meaning that they did not release the antibiotic into the solution during the 30 days of incubation, not even during shaking experiments.

Nihon Kokyuki Gakkai Zasshi, 2004 Mar, 42(3), 284 - 8
{A case of sarcoidosis with superior vena cava syndrome diagnosed by mediastinoscopy}; Mori H et al.; A bilateral hilar lymphadenopathy on the chest radiograph of a 30-year-old man was pointed out in a medical examination . Four months later, he was admitted to our hospital because of exacerbation of a bilateral hilar lymphadenopathy on the chest radiograph with high fever . Physical examination revealed a marked swelling of the face and upper arms as well as a dilated jugular vein . The fever, which was his chief complaint, responded to antibiotic therapy . A CT scan of the chest confirmed the presence of bilateral mediastinal lymphadenopathy and hilar lymphadenopathy, which caused pulmonary artery and superior vena cava stenosis . A superior vena cavagram demonstrated narrowing of the vessel . Mediastinoscopy was performed for definite diagnosis . Pathologic examination of the specimen revealed noncaseating epithelioid cell granuloma consistent with sarcoidosis . He was asymptomatic . Pulmonary function and arterial blood gas studies yielded almost normal results . A roentgenographic stage of intrathoracic change was Stage I . On the basis of these findings, he was observed carefully without systemic corticosteroid therapy . One month later, the swelling of his face and upper arms was improved, and the pulmonary functions and arterial blood gases remained almost normal . Only seven cases of sarcoidosis causing superior vena cava syndrome have been reported . This is the first case reported in Japan.

World J Gastroenterol, 2004 Apr 15, 10(8), 1115 - 20
C-reactive protein, procalcitonin, interleukin-6, vascular endothelial growth factor and oxidative metabolites in diagnosis of infection and staging in patients with gastric cancer; Ilhan N et al.; AIM: The current study was to determine the serum/plasma levels of VEGF, IL-6, malondialdehyde (MDA), nitric oxide (NO), PCT and CRP in gastric carcinoma and correlation with the stages of the disease and accompanying infection . METHODS: We examined the levels of serum VEGF, IL-6, PCT, CRP and plasma MDA, NO in 42 preoperative gastric cancer patients and 23 healthy subjects . There were infection anamneses that had no definite origin in 19 cancer patients . RESULTS: The VEGF levels (mean+/-SD; pg/mL) were 478.05+/-178.29 and 473.85+/-131.24 in gastric cancer patients with and without infection, respectively, and these values were not significantly different (P>0.05) . The levels of VEGF, CRP, PCT, IL-6, MDA and NO in cancer patients were significantly higher than those in healthy controls and the levels of CRP, PCT, IL-6, MDA and NO were statistically increased in infection group when compared with non-infection group (P<0.001) . CONCLUSION: Although serum VEGF concentrations were increased in gastric cancer, this increase might not be related to infection . CRP, PCT, IL-6, MDA and NO have obvious drawbacks in the diagnosis of infections in cancer patients . These markers may not help to identify infections in the primary evaluation of cancer patients and hence to avoid unnecessary antibiotic treatments as well as hospitalization . According to the results of this study, IL-6, MDA, NO and especially VEGF can be used as useful parameters to diagnose and grade gastric cancer.

Chem Commun (Camb), 2004 Apr 21, (8), 946 - 8 Epub 2004 Mar 16.
Total synthesis of the thiopeptide amythiamicin D; Hughes RA et al.; The first total synthesis of the thiopeptide antibiotic amythiamicin D is described.

Acta Clin Belg, 2003 Nov-Dec, 58(6), 360 - 1
Subacute endocarditis due to Erysipelothrix rhusiopathiae; Spiritus T et al.; Erysipelothrix rhusiopathiae is a rare cause of endocarditis . Most cases were observed in people working with animals . We report a case in a 45-year old man without any exposure to animals . He was admitted to our hospital because of dyspnoea . Blood cultures were drawn following fever on day 8 of hospitalisation . Erysipelothrix rhusiopathiae was cultured and echocardiography showed a vegetation on the mitral valve . Appropriate antibiotic therapy and surgical treatment led to a good outcome of the infection.

Eur J Intern Med, 2004 Feb, 15(1), 28 - 34
Clinical management of immunocompetent hospitalized patients with community-acquired pneumonia; Lamy O et al.; Background: Clinical practices and guidelines may differ regarding the management of inpatients with community-acquired pneumonia (CAP) . Methods: The management of 152 consecutive CAP inpatients (70+/-17 years) admitted to a teaching hospital was analyzed retrospectively and compared with published data and an evidence-based guideline developed at our institution . Results: Of the patients studied, 64% had a high prognostic score index (PSI), 14% were admitted to the ICU, and 4.6% died . Initially, patients received either a one-drug (47%) or a two-drug (53%) antibiotic regimen . None of the 20 PSI parameters, and neither the PSI nor admission to the ICU, was associated with the initial antibiotic regimen . Agreement between current practice and our guideline was low (kappa=0.16) . Following the recommendations would have led to a decrease of 51% in the initial two-drug regimen . The duration of i.v . antibiotherapy was higher in patients following the two-drug regimen (142+/-150 vs . 102+/-60 h, P<0.05) . Chest physiotherapy (CP) and bronchodilatators (BD) were prescribed in 72% and 54% of cases, respectively (median duration 10 days) . Conclusions: The variations observed in the clinical management of CAP inpatients were not in agreement with published guidelines . The overuse of a two-drug regimen, CP, and BD necessitates the development and implementation of evidence-based guidelines proposing detailed steps for the management of CAP inpatients.

J Infect, 2004 May, 48(4), 330 - 3
The effect of hyperbaric oxygen therapy on the bout of treatment for soft tissue infections; Sugihara A et al.; OBJECTIVES: Hyperbaric oxygen (HBO) therapy is often combined with antibiotic therapy for infections such as gas gangrene and osteomyelitis . Although numerous investigations have been undertaken to assess the effect of adjunctive HBO therapy on the treatment of infections, the bout of treatment has not been referred in the previous investigations . The purpose of this retrospective study was to evaluate the efficacy of HBO therapy on the bout of treatment for soft tissue infections . PATIENTS AND METHODS: In the period between 1994 and 2001, we treated 23 patients with soft tissue infections . Nine patients were treated with antibiotic chemotherapy alone, and 14 patients were treated with a combination of antibiotic chemotherapy and HBO therapy . The mean bout of treatment was compared between these two groups . RESULTS: The mean bout treated with a combination of antibiotic and HBO was significantly shorter than that with antibiotic alone . CONCLUSION: Our result indicates that HBO therapy combined with antibiotic therapy is able to shorten the bout of treatment for soft tissue infections . Therefore, we recommend HBO therapy combined with antibiotic therapy for soft tissue infections.

HNO . 2004 Apr 3; {Epub ahead of print}
{Perforation of the esophagus with a mediastinal abscessA late complication of surgical voice rehabilitation after laryngectomy}; Scheuermann K et al.; INTRODUCTION . Surgical voice rehabilitation after total laryngectomy is still only a partially solved problem . Because of easy handling and rare complications, the Provox voice prosthesis has become common in voice rehabilitation . CASE REPORT . The 69 year old patient underwent laryngectomy, selective bilateral neck dissection and the implantation of a Provox 1((R)) voice prosthesis because of a glottic squamous cell carcinoma (pT(4), pN(0), M(0)) . Postoperative healing ensued without any complications . During adjuvant radiochemotherapy, the patient developed distinctive cervical edema which led to a tilting of the Provox((R)) prosthesis . Due to a perforation of the posterior esophageal wall, the patient developed a pronounced mediastinal abscess which was relieved through a transcervical mediastinotomy . Antibiotic therapy led to a partial remission of the symptoms . CONCLUSION . Severe complications may not only occur during the early phase of surgical voice rehabilitation, but also at a much later stage, after completion of the healing process . A voice prosthesis which is too long or generates pressure from a radiogenic edema, cannula and finger pressure used to close the tracheostoma is transmitted through the prosthesis and may lead to a perforation of the posterior esophageal wall . In particular, when the tissue is injured during the course of radiotherapy, this type of complication should be taken into consideration.

J Vasc Interv Radiol, 2004 Apr, 15(4), 327 - 34
Diagnosis and management of long-term central venous catheter infections; Hall K et al.; The pathogenesis, diagnosis, and management of central venous catheter infections differ between short-term and long-term catheters . This review summarizes available data regarding the diagnosis and management of catheter-related bloodstream infections (CRBSIs) associated with long-term catheters . A review of various diagnostic modalities is provided, including methods of CRBSI diagnosis for catheters that are retained . Management of CRBSIs for long-term catheters is also addressed, with an emphasis on differentiating infections that require catheter removal from those that may allow catheter salvage . Data regarding catheter salvage with use of antibiotic lock therapy are also reviewed.

Acad Emerg Med, 2004 Apr, 11(4), 371 - 7
Compliance with the Centers for Disease Control and Prevention recommendations for the diagnosis and treatment of sexually transmitted diseases; Kane BG et al.; Little is known about gaps in quality and the extent to which clinical standards are used in emergency department (ED) practice . OBJECTIVES: To determine whether ED practitioners comply with the Centers for Disease Control and Prevention (CDC) recommendations for diagnosing and treating sexually transmitted diseases (STDs) . METHODS: A retrospective chart review of ED visits was conducted at an urban teaching hospital . Using ICD-9 codes, urethritis, cervicitis, pelvic inflammatory disease (PID), gonorrhea, and chlamydia cases seen from May 1, 2000, to February 28, 2001, were identified . Documentation of components of the history, physical examination, diagnostic testing, prescribed antibiotics, and discharge instructions necessary to comply with the CDC guidelines were abstracted . This set of comprehensive criteria was compared with a less stringent subset of selected criteria . RESULTS: Two hundred forty-six patient visits were identified, and 203 (83%) were included . Forty-eight men and 155 women were included: 48 (24%) with urethritis, 34 (17%) with cervicitis, and 121 (60%) with PID . For urethritis, cervicitis, and PID, respectively, there was documentation of compliance with indicators related to the following: history 73%, 15%, and 14%; physical examinations 63%, 15%, and 22%; diagnostic testing 79%, 71%, and 71%; antibiotic use 33%, 32%, and 32%; and safe sex instructions 50%, 18%, and 15% of the time . Men were more likely to receive safe sex instructions (p < or = 0.01) . Total (100%) compliance in all five domains occurred 8% of the time for urethritis, 3% for cervicitis, and never for PID . The rates of 100% compliance were not significantly different when a subset of selected criteria was used . CONCLUSIONS: Deficits in adherence to recommended guidelines for the diagnosis and treatment of STDs exist in ED practice.

Am J Med, 2004 Apr 15, 116(8), 529 - 35
Performance of a bedside C-reactive protein test in the diagnosis of community-acquired pneumonia in adults with acute cough; Flanders SA et al.; PURPOSE: To evaluate the performance of a rapid, bedside whole blood C-reactive protein test as a diagnostic test for pneumonia in adults . METHODS: We enrolled consecutive adults who presented with acute cough (duration < or =3 weeks) . A fingerstick blood specimen for C-reactive protein level was obtained . Patients also provided information about demographic characteristics and symptoms . Physical examination findings, diagnoses, and treatments were abstracted from the medical record; illness duration and subsequent office visits were determined with follow-up telephone calls . A clinical prediction rule for pneumonia was calculated for each patient and compared with C-reactive protein levels . RESULTS: Twenty (12%) of the 168 patients in the study had radiographic evidence of pneumonia . Median C-reactive protein levels were significantly higher for patients with pneumonia than in the remaining patients (60 mg/L vs . 9 mg/L, P <0.0001) . The area under the receiver operating characteristic (ROC) curve for C-reactive protein level as a predictor of pneumonia was 0.83 . C-reactive protein level and the clinical prediction rule were independently associated with pneumonia, yielding a combined area under the ROC curve of 0.93 . C-reactive protein level was not associated with hospitalization or resolution of symptoms . CONCLUSION: C-reactive protein levels could be a valuable addition to clinical prediction rules for pneumonia . A C-reactive protein level > or =100 mg/L might be a useful indication for chest radiography or empiric antibiotic therapy when the diagnosis of pneumonia is in doubt.

J Chromatogr B Analyt Technol Biomed Life Sci, 2004 Apr 25, 803(2), 311 - 5
Determination of derivatized l-alanosine in plasma by liquid chromatography-tandem mass spectrometry; Gantverg A et al.; A sensitive method was developed for quantitation of the cytotoxic antibiotic l-alanosine in human plasma . Alanosine was extracted from plasma by anion-exchange solid phase extraction, derivatized with dansyl chloride and analyzed by liquid chromatography-tandem mass spectrometry using atmospheric pressure chemical ionization in negative mode . Dansylation led to 50-fold improvement of method sensitivity over non-dansylated alanosine with a resulting 20 ng/ml limit of alanosine quantitation in plasma being achieved . The method was validated and applied for clinical studies of alanosine administered to cancer patients.

Neurol Clin, 2004 May, 22(2), 329 - 45
Management of perioperative infectious complications in the neurologic patient; Cardona-Bonet LL et al.; Although most neurosurgeries are considered "sterile" procedures, anti-biotic prophylaxis is favored in the literature because of the potential for serious complications related to the central nervous system . There is a paucity of literature addressing the management of infectious complications related to neurostimulators and intraspinal/epidural catheters and pump; therefore, further studies are needed to develop standard protocols of care . Finally, perioperative complications in the patient undergoing a neuro-surgical procedure are similar to those undergoing any surgery, but have a higher potential for morbidity and mortality because of the central nervous system . The skill of the surgeon, care of the perioperative team, and knowledge of the neurologist remain the most important factors in the prevention, early recognition, and intervention of these complications.

Clin Liver Dis, 2004 Feb, 8(1), 151 - 66
Postoperative jaundice; Faust TW et al.; Abnormal LCTs after surgery are common, and consultants are frequently called on to evaluate critically ill patients with abnormal tests . All patients undergoing consideration for elective surgery and a history of either acute or chronic liver disease require careful presurgical evaluation . A thorough history and physical examination, complete blood count, routine electrolytes, LCTs, and a coagulation profile should be ordered . For patients with marginal hepatic reserve, it is important that patient well-being be maximized before any elective operation . The type of surgery to be performed should also be reviewed . All patients with postoperative jaundice should be evaluated for a history of liver disease . The consultant should also review the surgical procedure performed, anesthetic agents administered, other medications used, and whether blood products were given during the perioperative and postoperative periods . The pattern and timing of LCT abnormalities may also give a clue to the underlying disorder . As in the preoperative assessment, a routine complete blood count,electrolyte panel, LCTs, and coagulation profile should be ordered . Unconjugated hyperbilirubinemia can develop as a consequence of blood transfusions, underlying hemolytic disorders, resorbing hematomas, drug effects, or Gilbert's syndrome . A haptoglobin, reticulocyte count, LDH, and Coomb's test should be considered in patients with unconjugated hyperbilirubinemia . Treatment is directed toward the underlying condition . Conjugated hyperbilirubinemia can occur as a result of either intrahepatic or extrahepatic disorders . Markedly abnormal aminotransferases and LDH in conjunction with a normal abdominal ultrasound scan suggest ischemic liver injury, drug-induced hepatitis, or viral infections of the liver . Treatment entails restoration of hepatic perfusion, removal of offending medications, and supportive care or antiviral agents, respectively . Extrahepatic biliary obstruction must be considered in all patients with conjugated hyperbilirubinemia . Abdominal sonography is the best screening test to assess for obstruction . Patients with common bile duct stones usually require ERCP with sphincterotomy and stone removal . Biliary strictures or leaks may require ERCP with balloon dilation of strictures or stent placement for strictures and leaks; percutaneous drainage of bilomas in combination with broad-spectrum antibiotic agents is recommended for patients with bile leaks and large intra-abdominal fluid collections . Surgery may be required for patients with strictures or leaks not amenable to either endoscopic or percutaneous intervention or for patients who have transected bile ducts after laparoscopic cholecystectomy . Medication effects, benign postoperative jaundice, sepsis, TPN, and acalculous cholecystitis are responsible for intrahepatic cholestasis and conjugated hyperbilirubinemia . Treatment includes removal of offending drugs, supportive care, broad-spectrum antibiotic agents with drainage of infected fluid collections, adjustment of TPN, and either cholecystectomy or cholecystostomy, respectively.

Hindustan Antibiot Bull, 2002 Feb-Nov, 44(1-4), 47 - 8
Invitro drug sensitivity of Trichophyton species against griseofulvin and ketoconazole; Dodia S et al.; The in vitro activity of griseofulvin and ketoconazole was investigated against Trichophyton mentagrophytes (Robin) Blanchard and T . Simii (Pinoy) Stockdale, Mackenzie and Austwick . A gradual decrease in growth was observed with increase in concentration of both antibiotics . Ketoconazole was the more effective antibiotic than griseofulvin as it observed to inhibit > 50% mycelial weight even at a lower concentration of 100 ppm . While griseofulvin was effective to cause > 50% growth inhibition only at higher dosage of 400 ppm.

J Microbiol Immunol Infect, 2004 Feb, 37(1), 50 - 6
Discontinuation of secondary prophylaxis in AIDS patients with disseminated non-tuberculous mycobacteria infection; Liao CH et al.; From June 1994 to June 2002, disseminated infections due to non-tuberculous mycobacteria (NTM) were diagnosed in 42 of 716 (5.9%) non-haemophiliac HIV-infected patients aged > or =15 years who were treated at National Taiwan University Hospital . The median age of these patients was 35 years (range, 27 to 60 years) . The median CD4+ cell count and plasma viral load at the time of diagnosis of disseminated NTM infections were 8 x 10(6)/L (range, 0 to 892 x 10(6)/L) and 37,600 copies/mL (range, <400 to >750,000 copies/mL), respectively . The nadir CD4+ count during the observation period was 6 x 10(6)/L (range, 0 to 30 x 10(6)/L) . The species of NTM isolated included Mycobacterium avium complex (MAC) {n = 35}, Mycobacterium kansasii (4), Mycobacterium chelonae (1), Mycobacterium abscessus (1), and unidentified NTM (3) . Co-infection with 2 species of NTM was diagnosed in 2 patients . NTMs were isolated from blood (n = 18), liver (18), lymph node (12), bone marrow (10), cerebral spinal fluid (1), ascites (1), and pericardial effusion (1) . The median duration of antimycobacterial therapy of the 42 patients was 7 months (range, 0 to 24 months) . Mortality during the study period was greater in the patients enrolled before highly active antiretroviral therapy (HAART) was introduced (14 of 15, 93%) than in those who received HAART (9 of 27, 33%) . As of December 31, 2002, 15 patients (35.7%) had discontinued secondary prophylaxis against disseminated NTM infections when their median CD4+ count had increased to 119 x 10(6)/L (range, 25 to 465 x 10(6)/L), and 86.7% (13/15) of the patients had achieved an undetectable plasma viral load after HAART . During the median observation duration of 12 months (range, 2 to 57 months), none of the 15 patients had relapse of disseminated NTM infections . Our findings indicate that disseminated NTM infections without primary prophylaxis were associated with a high mortality rate, especially before HAART became available . In patients who received HAART and had a favorable response with viral suppression and immune restoration, discontinuation of secondary prophylaxis against disseminated NTM infections was safe.

AIDS, 2004 Apr 9, 18(6), 933 - 8
Higher rates of post-partum complications in HIV-infected than in uninfected women irrespective of mode of delivery; Fiore S et al.; OBJECTIVE: To inform the debate on the use of elective caesarean section (CS) delivery in HIV-infected women, we investigated the occurrence of clinical events in the immediate post-partum period in women delivering in 13 European centres . DESIGN: Two separate matched case-control studies (vaginal and elective CS deliveries) among infected women (cases) and uninfected controls delivering between 1992 and 2002 . METHODS: The prevalence of minor and major post-partum complications was assessed overall for infected and uninfected women; within mode of delivery group (vaginal/CS) the complication rates of infected cases were compared with uninfected controls in a matched analysis . RESULTS: Overall complication rates were 29.2% (119 of 408) for HIV-infected women, 19.4% (79 of 408) for uninfected women, 42.7% (135 of 316) for CS deliveries and 12.6% (63 of 500) for vaginal deliveries . There were no major complications in women delivering vaginally; but, compared with controls, HIV-infected cases were at increased risk of puerperal fever {odds ratio (OR), 4.5; 95% confidence interval (CI), 1.55-13.07), especially after medio-lateral episiotomy . In the CS group, there were six major complications (five among cases, one control) (OR, 5.1; 95% CI, 0.58-45) and cases had an increased risk of minor complications (OR, 1.51; 95% CI, 1.22-2.41) compared with controls, mainly anaemia not requiring blood transfusion . CONCLUSION: HIV-infected pregnant women are at increased risk of post-partum complications regardless of mode of delivery, but modification of clinical practice, particularly use of prophylactic antibiotics, would reduce this risk . Infected women should be informed about risks of vertical transmission and post-partum complications, and be involved in mode of delivery decisions.

Pediatrics, 2004 Apr, 113(4), e380 - 4
Chronic recurrent multifocal osteomyelitis of the spine and mandible: case report and review of the literature; Chun CS; At initial presentation, chronic recurrent multifocal osteomyelitis may mimic acute hematogenous osteomyelitis; however, cultures of affected bone are sterile . Nuclear scintigraphy identifies additional foci of involvement that present concurrently or sequentially . Unlike acute bacterial osteomyelitis, chronic recurrent multifocal osteomyelitis seems unaffected by antibiotic therapy and typically responds to treatment with antiinflammatory drugs . Surgical decortication has been reported for refractory cases . The case presented here illustrates the rare involvement of the mandible after initial presentation in the spine of a 4-year-old girl and the refractory nature of the disease over 6 years despite treatment with various medical and surgical therapies.

Pediatrics, 2004 Apr, 113(4 Suppl), 1120 - 7
Teeth; Billings RJ et al.; Common environmental chemicals, drugs, or physical agents can adversely affect human teeth during their embryonic development and after their eruption into the oral cavity . One of the more common elemental toxicants is lead . Teeth are known to accumulate lead during their development . Both animal and human studies have shown that teeth with high lead levels are generally more susceptible to dental caries . Similarly, although inorganic fluorides have long been recognized for their potential to prevent dental caries, exposure to excessive amounts of fluoride when enamel is forming often leads to a type of enamel hypoplasia referred to as dental fluorosis or mottled enamel . Teratogenic agents, such as tetracyclines, a class of antibiotic drugs commonly administered to infants and children, will often result in the discoloration of tooth enamel when prescribed during tooth development . It has recently been suggested that childhood exposure to passive smoking increases the risk for dental caries . Environmental tobacco smoke has previously been linked to periodontal disease in adults . However, this is the first report of an association between passive tobacco smoke and increased susceptibility to dental caries . Last, an often-overlooked source of damage to teeth among all age groups after their eruption into the oral cavity is physical trauma from a variety of sources, especially sports-related injuries . Epidemiologic data suggest that up to one third of all dental injuries are sports related.

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